Week 1:

 Fertilization – fusion of sperm & oocyte; requires ~24 hrs

o Ampulla of uterine tube
o Sperm passes corona radiata and zona pellucida to get to oocyte
o Zona pellucida becomes rigid – prevents polyspermy
o Secondary oocyte completes 2nd meiotic division; expels 2nd polar body
o Male & female pronuclei meet in center of oocyte
 Chromosomes intermingle at metaphase of 1st mitotic division of zygote; end of
fertilization
 Cleavage – initiated by fertilization stimulating zygote to undergo rapid cell divisions; occurs as zygote
passes down uterine tube
o Zygote divides to 2 daughter cells ~30 hrs after fertilization (blastomeres)
o Further divisions continue creating smaller & more numerous blastomeres
o Morula formed at day 3; 16 cell blastomeres
 Enters uterus as it forms
o Fluid from uterine cavity enters morula (day 4) to create trophoblast (placenta) & inner cell mass
(embryo) layers
 Forms blastocyst cavity; converts morula to blastocyst
o Inner cell mass projects into blastocyst cavity; trophoblast forms wall of blastocyst
o Zona pellucida degenerates/disappears ~2 days later (day 4-5)
 Implantation initiation – day 5-6
o Trophoblastic cells invade endometrial epithelium while trophoblast layer differentiates into
cytotrophoblast (inner) & syncytiotrophoblast (outer; multinucleated; no cellular boundaries)
layers
 Syncytiotrophoblast begins to grow into endometrial epithelium & invades stroma
 Cytotrophoblast forms new cells that migrate into syncytiotrophoblast
o As blastocyst is implanting, inner cell mass differentiates
 Embryonic endoderm (flat layer of cells) appears on surface of ICM; faces blastocyst
cavity (ventral surface of ICM) ~day 7
 Bilaminar embryonic disc composed of epiblast (high columnar; future ectoderm &
mesoderm) & hypoblast (cuboidal cells of embryonic ectoderm)
o Amniotic cavity (by day 8; b/w ICM & invading trophoblast), yolk sac, connecting stalk, & chorion
develop
Week 2:
 Implantation continues – day 7-12
o Conceptus receives nourishment from endometrial tissues at this point
o Amnion (thin epithelial cells) forms roof of amniotic cavity; embryonic epiblast forms floor
(continuous w/ amnion peripherally)
o Cells delaminate from cytotrophoblast & form thin exocoelomic membrane extending around
inner cell wall of blastocyst cavity & encloses a 2nd cavity – primitive yolk sac
 Further delamination of trophoblastic cells gives rise to extraembryonic mesoderm
around amnion & primitive yolk sac
o ~day 9, lacunae appear in syncytiotrophoblast & soon become filled w/ maternal blood from
ruptured capillaries & secretions from eroded endometrial glands
o Eventually, endometrium forms maternal part of placenta & trophoblast forms fetal part (villous
chorion)
o Conceptus lies under endometrial epithelium ~day 10 (indicated by closing plug; day 12)
o Lacunar networks have now formed; developed first at embryonic pole & form primitive
intervillous spaces of the placenta
o Changes in trophoblast & endometrium occur & the extraembryonic mesoderm increases
(isolated coelomic spaces visible w/in mesoderm by day 11)
 Coelomic spaces fuse to form large isolated cavities of extraembryonic coelom
o Embryonic endoderm extends beyond rim of embryonic disc & along inside of dorsal part of
primitive yolk sac
 o Proliferation of cytotrophoblast produces local masses/clumps that extend into
syncytiotrophoblast & indicate first stage of chorion villous (primary villi) development (day 13-
14)
o Embryonic coelom surrounds amnion & yolk sac except where amnion is attached to
trophoblast by the connecting stalk
 Primitive yolk sac decreases in size during coelom formation & a smaller secondary yolk
sac develops
o Coelom splits the extraembryonic mesoderm into somatic (covers amnion & lines trophoblast) &
splanchnic (covers yolk sac)
 Somatic mesoderm & trophoblast constitute the chorion
 Forms chorion sac w/ the embryo and its amnion & yolk sac are suspended by
the connecting stalk w/in it
 Coelom becomes cavity of chorionic sac
o Embryo is still in form of a flat bilaminar embryonic disc at this point but the endodermal cells in
a localized area have become columnar
 Form thickened circular area (prochordal plate)
 Prochordal plate indicates future site of mouth & serves as an important
organizer of the head region
o Implantation summary:
 1) days 4-5: zona pellucida disappears
 2) days 5-6: blastocyst attaches to endometrial epithelium
 3) days 7-8: trophoblast erodes surface epithelium & endometrial stroma as it
differentiates to cytotrophoblast & syncytiotrophoblast layers
 4) day 9: lacunae appear in syncytiotrophoblast
 5) days 9-10: blastocyst sinks beneath surface of endometrial epithelium
 6) days 10-11: lacunar network forms
 7) days 11-12: trophoblast invades endometrial sinusoids & establishes uteroplacental
circulation
 8) days 12-13: defect in surface epithelium disappears
 9) days 13-14: marked decidual reaction in endometrium around conceptus
Week 3:
 Formation of trilaminar embryo (germ layers)
 Primitive streak development – day 15
o A thickened linear band of embryonic epiblast appears caudally in midline of dorsal aspect of
embryonic disc (primitive streak)
 Once primitive streak is visible, it is possible to identify directional surfaces/axis
o Primitive streak elongates by addition of cells at its caudal end; cranial end thickens to form a
primitive knot/node
o A narrow primitive groove develops in primitive streak & continues into a depression in primitive
knot – primitive pit
 Intraembryonic mesoderm – day 16
o Intraembryonic mesoderm appears from cells produced by the primitive streak
 The epiblast layer is now referred to as the embryonic ectoderm
 Cells of epiblast migrate to primitive streak & enter primitive groove and then migrate
laterally b/w the ectoderm & endoderm to become organized into intraembryonic
mesoderm layer
o Cells from intraembryonic mesoderm migrate to become mesenchymal cells
 Mesenchymal cells can differentiate to fibroblasts, chondroblasts, or osteoblasts
 Notochord – day 16
o Cells from primitive knot migrate cranially & form midline cord – notochordal process
 Grows b/w ectoderm & endoderm until it reaches prochordal plate (can’t extend further
b/c prochordal plate is firmly attached to overlying ectoderm, forming the
buccopharyngeal membrane)
o Caudal to primitive streak is cloacal membrane where embryonic disc remains bilaminar
(prevents migration of mesenchymal cells)
 Also remains bilaminar at buccopharyngeal membrane
 o Notochord is a cellular rod developed from notochordal process & defines primitive axis of
embryo
o As notochordal process develops, primitive pit extends into it & forms lumen (notochordal canal)
o Notochord develops as notochordal process floor fuses w/ endoderm & then fused regions
degenerate causing openings in floor of process, bringing notochordal canal in contact w/ yolk
sac
 Openings become confluent & notochordal canal floor disappears
 Remains of notochordal process form flattened grooved plate (notochordal plate) which
begins to fold at the cranial end to form the notochord
 Endoderm then again becomes continuous ventral to notochord (~day 18)
 Neural tube – day 18
o As notochord develops, ectoderm over it thickens to form neural plate
 Neural plate formation is induced by developing notochord & the paraxial mesoderm on
each side
o Ectoderm of neural plate (neuroectoderm) gives rise to CNS (brain & spinal cord)
o Neural plate first appears cranial to primitive knot, dorsal to notochordal process & adjacent
mesoderm
o As notochordal process elongates, neural plate broadens & extends cranially as far as the
buccopharyngeal membrane
o ~day 18, neural plate invaginates along central axis to form neural grooves w/ neural folds on
each side
o Neural folds have begun to move together & fuse by the end of the third week converting the
neural plate to the neural tube
 The neuroectodermal cells that don’t become incorporated into neural tube become
neural crest cells over the neural tube
o During formation of notochord & neural tube, intraembryonic mesoderm on each side of them
thickens to form longitudinal columns of paraxial mesoderm which is continuous laterally w/
intermediate mesoderm which gradually thins laterally into lateral mesoderm
 Lateral mesoderm is continuous w/ extraembryonic mesoderm on yolk sac & amnion
 Somites – day 20
o Paraxial mesoderm begins to divide into paired cuboidal bodies (somites)
o Somites give rise to most of the axial skeleton & associated musculature as well as much of the
dermis of the skin
o The first pair of somites forms a short distance caudal to cranial end of notochord & subsequent
pairs form in a craniocaudal sequence
 Eventually form 44 pairs
 Third week continued
o Intraembryonic coelom arises in lateral mesoderm and cardiogenic mesoderm
 Coalesce to form a single cavity that gives rise to the body cavities
o Blood vessels first appear on yolk sac, allantois, & in the chorion & develop w/in embryo after
 Blood islands form w/in aggregations of mesenchyme which soon become lined w/
endothelium & unite w/ other spaces to form primitive cardiovascular system
 Primitive blood cells are formed primarily from endothelial cells of blood vessels in yolk
sac & allantois
o Primary villi become secondary villi as they acquire mesenchymal cores
 By end of 3rd week capillaries develop in villi and are referred to as tertiary villi
 Cytotrophoblastic extensions from villi mushroom out & join to form cytotrophoblastic
shell that anchors chorionic sac to endometrium
 Surface area of chorion is greatly increased for embryonic-maternal exchange
Weeks 4-8 (Embryonic Period):
 Most important period of development b/c all major external & internal structures are developed
o Exposure to teratogens may cause major congenital malformations
 Folding of the embryo
o Significant event in establishment of general body form is folding of the flat trilaminar embryonic
disc into a cylindrical embryo
 o Folding in longitudinal & transverse planes is caused by rapid growth of embryo especially at
neural tube
o Formation of longitudinal & transverse folds is a simultaneous process of constriction at junction
of embryo & yolk sac
o Folding in longitudinal plane produces head & tail folds that result in cranial & caudal regions
swinging ventrally
o Head Fold:
 At end of 3rd week neural folds begin to develop into the brain & project dorsally into
amniotic cavity
 Forebrain grows cranially beyond buccopharyngeal membrane & overhangs primitive
heart
 Septum transversum (mesoderm cranial to pericardial coelom), heart, pericardial
coelom, & buccopharyngeal membrane turn under onto ventral surface
 During folding part of the yolk sac incorporates into embryo as the foregut b/w brain &
heart & ends blindly at buccopharyngeal membrane
 Buccopharyngeal membrane separates foregut from stomodeum (primitive mouth)
 After folding, septum transversum lies caudal to heart & develops into diaphragm
 Head fold affects arrangement of intraembryonic coelom – the pericardial coelom lies
ventrally & pericardioperitoneal canals run dorsally over septum transversum & join
peritoneal coelom
 At this point, peritoneal coelom on each side communicates w/ extraembryonic
coelom
o Tail Fold:
 Occurs a little later than cranial end
 Tail fold results from dorsal & caudal growth of neural tube
 As embryo grows, tail region projects over cloacal membrane (membrane eventually lies
ventrally)
 During folding, part of yolk sac incorporates into embryo as hindgut
 Terminal end of hindgut dilates slightly to form cloaca – it is separated from amniotic
cavity by cloacal membrane
 Before folding, primitive streak lies cranial to cloacal membrane – after folding, it lies
caudal to it
 Connecting stalk now attaches to ventral surface of embryo & allantois is partially
incorporated into embryo
o Transverse Folding:
 Produces right & left lateral folds
 Each lateral body wall/somatopleure folds toward midline, rolling edges of embryonic
disc ventrally & forms cylindrical embryo
 As lateral & ventral walls form, part of yolk sac incorporates into embryo as midgut
 Connection of midgut w/ yolk sac is reduced to narrow yolk stalk/vitelline duct
 After folding, region of attachment of amnion to embryo is reduced to umbilicus on the
ventral surface
 As midgut separates from yolk sac, it becomes attached to dorsal abdominal wall by
dorsal mesentery
 As umbilical cord forms, ventral fusion of lateral folds reduces communication b/w intra-
& extra- embryonic coeloms
 As amniotic cavity expands & obliterates extraembryonic coelom, amnion forms an
external investment/covering for the umbilical cord
 Germ layer derivatives
o Embryonic ectoderm, mesoderm, & endoderm give rise to all tissues/organs of embryo
o Ectoderm: CNS; PNS; sensory epithelia of eye, ear, & nose; epidermis & its appendages (hair &
nails); mammary glands; pituitary gland; subcutaneous glands; enamel of teeth
o Mesoderm: cartilage; bone/CT; muscle; heart; blood & lymph vessels/cells; kidneys; gonads &
genital ducts; serous membranes lining body cavities; spleen; cortex of adrenal gland
 o Endoderm: epithelial lining of GI & respiratory tracts; parenchyma of tonsils, thyroid,
parathyroids, thymus, liver, & pancreas; epithelial lining of urinary bladder & urethra; epithelial
lining of tympanic cavity, antrum, & auditory tube
 Control of development:
o Development results from genetic plans contained in chromosomes
o Defective plans – abnormal # of chromosomes, translocations, gene mutations, etc. – result in
maldevelopment
o Abnormal development may be caused by environmental factors
 Most developmental processes depend on a precisely coordinated interaction of genetic
& environmental factors
o Induction – for a limited time during early development, certain embryonic tissues markedly
influence the development of adjacent tissues; the tissues producing these influences or effects
= inductors
 Involves 2 tissues: the inducing tissue & the induced tissue
 In order to induce, an inductor must be close to the other tissue
 Primitive streak, notochord, & paraxial mesoderm act as primary inducers of CNS
 Once the basic plan has been established by primary inducers, a chain of secondary
inductions occurs
 Week 4:
o Days 22-23: embryo is almost straight & somites produce surface elevations; neural tube is
closed opposite of somites but widely open at rostral & causal neuropores
o Day 24: the 1st (mandibular) & 2nd (hyoid) pharyngeal arches are distinct
 mandibular process of 1st arch will give rise to lower jaw & maxillary process will
contribute to upper jaw
 a slight curve is produced in embryo by head & tail folds & the heart produces a large
ventral prominence
o ~day 26: 3 pairs of pharyngeal arches visible
 rostral neuropore is closed
 forebrain produces prominent elevation on head
 continued longitudinal folding has given embryo C-shaped curvature
 narrowing of connection b/w yolk sac & embryo caused by transverse folding
 arm buds become recognizable as small swellings on ventrolateral body walls
 otic pits (inner ear) clearly visible
o ~day 28: 4th pair of pharyngeal arches present
 leg buds present
 lens placodes visible on side of head
 Week 5:
o Growth of head exceeds that of other regions; caused mainly by rapid development of brain
o Face soon contacts heart prominence
o 2nd hyoid arch overgrows 3rd & 4th arches forming the cervical sinus
o forelimbs begin to show regional differentiation as hand plates develop
 Week 6:
o Forelimbs show considerable regional differentiation
o Elbow & wrist become identifiable
o Finger rays present
o Swellings develop around groove b/w first 2 pharyngeal arches
 Groove becomes external acoustic meatus
 Swellings eventually fuse to form auricle of ear
o Eye becomes more obvious
o Trunk & neck have begun to straighten
o Somites visible in lumbosacral region until middle of week 6
 Week 7:
o Communication b/w gut & yolk sac reduced to yolk stalk
o Intestines enter extraembryonic coelom in proximal portion of umbilical cord
o Forelimbs project over heart
o Notches appear in finger rays
  Week 8:
o Fingers are short & noticeably webbed
o Notches visible b/w toe rays
o Tail bud still visible
o Fingers have lengthened by end of week
o Evidence of tail bud disappears by end of week 8
o Head is rounder & erect
o Eyelids are obvious
o Auricles of ears assume final shape but still low-set
Week 9 – Birth (Fetal Period):
 The name change from zygote to fetus signifies that the zygote (single cell) is a recognizable human
 Fetal period concerned w/ growth & differentiation of tissues & organs that started developing during
embryonic period
 Body growth is rapid during weeks 9-12
 Weeks 9-12:
o At beginning of 9th week, head constitutes half of fetus
o Face is broad, eyes separates, ears still low-set; fused eyelids
o At end of 12th week, upper limbs almost at full length
o Male/female genitalia appear similar until end of 9th week
o Mature fetal form not established until 12th week
 Weeks 13-16:
o Rapid growth
o Legs have lengthened
o Skeleton ossification rapidly progressed
o Scalp hair patterning determined; gives clue to early fetal brain development
 Weeks 17-20:
o Lower limbs reach final proportions
o Fetal movements felt by mother
o Eyebrows/head hair visible
o Brown fat forms
 Weeks 21-25:
o Substantial weight gain
o Skin is wrinkled; transparent
o Respiratory system still too immature to survive premature birth
 Weeks 26-29:
o Fetus could now survive premature birth
o Lungs & pulmonary vascularity developed adequately enough to provide gas exchange
o CNS mature enough where it can direct rhythmic breathing movements & control body
temperature
o White fat increases
 Weeks 30-34:
o Skin is pink & smooth
o Arms & legs have chubby appearance
 Weeks 35-38:
o “Finishing” period
Fetal Membranes & Placenta:
 Chorion, amnion, yolk sac, & allantois = embryonic/fetal membranes
o Develop from zygote but don’t form parts of embryo (except portions of yolk sac & allantois)
 Placenta has 2 components – fetal portion (developed from chorion) & maternal portion (formed by
endometrium)
 Fetal membranes & placenta fxns: protection, nutrition, respiration, & excretion
 Decidua = maternal portion
o 3 portions identified according to relation to implantation site:
 1) part underlying conceptus & forming maternal portion of placenta = decidua basalis
 2) superficial portion overlying conceptus = decidua capsularis
 3) all remaining uterine mucosa = decidua parietalis
  Up until 8th week, villi cover entire surface of chorionic sac
o As sac grows, villi associated w/ decidua capsularis become compressed & blood supply
reduced
 Villi begin to degenerate producing avascular bare area – chorion leave
o Villi associated w/ decidua basalis increase in number, branch profusely, & enlarge – become
known as villous chorion/chorion frondosum (forms fetal portion of placenta)
o Maternal portion of placenta (decidua basalis) has compact layer – decidual plate
 Final shape of placenta determined by form of persistent area of villi – usually circular, giving placenta a
discoid shape
o As villi invade decidua basalis, they leave placental septa – divides fetal part of placenta into
cotyledons – consists of 2 or more main stem villi & their branches
 Blood-filled intervillous spaces (from lacunae in syncytiotrophoblast) enlarge at expense of decidua
basalis during invasion of trophoblast
o Spaces form a large blood sinus (intervillous space) bound by chorionic plate & decidua basalis
o Divided into compartments by placental septa; since septa don’t reach chorionic plate, there is
communication b/w intervillous space of different compartments
o Intervillous space drained by veins that cover entire surface of decidua basalis
 As conceptus gets larger, decidua capsularis bulges into uterine cavity & eventually fuses w/ decidua
parietalis – obliterates uterine cavity
o Reduced blood supply causes decidua capsularis to degenerate & disappear (week 22)
 Fetal placenta (villous chorion) anchored to maternal portion of placental portion (decidua basalis) by
cytotrophoblastic shell to which the main stem villi are anchored (anchoring villi)
 Placenta fxns: metabolism, transfer, endocrine activity
o Synthesizes glycogen, cholesterol, fatty acids, & serves as source of nutrients & energy for
embryo
o All materials transported across placental membrane by simple diffusion, facilitated diffusion,
active transport, or pinocytosis
 Gases cross membrane by simple diffusion
 Water soluble vitamins cross membrane quicker than fat soluble vitamins
 Glucose is quickly transferred
 Electrolytes are freely exchanged across membrane
 Passive immunity conferred to fetus by transfer of maternal antibodies
 Because amnion is attached to margins of embryonic disc, its junction w/ embryo becomes located on
ventral surface as a result of folding
o As amniotic sac enlarges, gradually obliterates chorionic cavity & sheaths umbilical cord (forms
epithelial covering)
 Cells of amnion have microvilli – fluid transfer
 Embryo floats freely in amniotic fluid (suspended by umbilical cord)
o Amniotic fluid: permits symmetrical external growth of embryo, prevents adherence of amnion to
embryo, cushions embryo against jolts by distributing impacts the mother may receive, helps
control embryo’s body temperature, & enables fetus to move freely which aids in
musculoskeletal development
Teratology:
 Causes of congenital malformations divided into genetic factors (chromosomal abnormalities/mutant
genes) & environmental factors
 Malformations caused by genetic factors – chromosome complements are subject to two kinds of
changes, numerical & structural
o Mechanism initiated by the genetic factor may be identical/similar to causal mechanism initiated
by an environmental teratogen
o Females have 22 pairs of autosomes + 2 X chromosomes
o Males have 22 pairs of autosomes + 1 X & 1 Y chromosome
o Aneuploidy = any deviation from diploid number of 46 chromosomes
o Monosomy = embryos missing chromosome
 Usually die
 Turner syndrome
o Trisomy = 3 chromosomes present instead of usual pair
  Cause is usually nondisjunction – results in germ cell w/ 24 instead of 23 chromosomes,
& zygote w/ 47 chromosomes
 Most common condition = down syndrome (3 #21 chromosomes present)
 Klinefelter syndrome = XXY male; usually infertile
o Polyploidy = contain multiples of the haploid number of chromosomes; significant cause of
spontaneous abortion
o Most structural abnormalities result from chromosome breaks induced by various environmental
factors
 Translocation = transfer of a piece of one chromosome to a nonhomologous
chromosome
 Deletion = chromosome breakage resulting in portion of chromosome being lost
 Duplication = duplicated portion of chromosome w/in a chromosome or attached to a
chromosome or as a separate fragment; no loss of genetic material
 Environmental factors = teratogens; most common malformations result from complex interactions of
genetic & environmental factors
o Teratogens may induce congenital malformations when tissues/organs are developing
 Embryonic organs most sensitive
o Environmental disturbances during 1st 2 weeks after fertilization may interfere w/ implantation of
blastocyst or cause early death/abortion of embryo
 Rarely cause congenital malformations
o May cause mitotic nondisjunction during cleavage resulting in chromosomal abnormalities that
then cause congenital malformations
o Physiological defects, minor morphological abnormalities, & functional disturbances likely to
result from disturbances during fetal period
o Radiation – produce abnormalities of CNS, eyes, may cause mental retardation
o Rubella virus – may cause cataracts, deafness, & cardiac malformations
o Thalidomine – skeletal & other malformations; meromelia, amelia
Pharyngeal/Branchial Apparatus:
 Pharyngeal apparatus = arches, pouches, grooves, & membranes
 Most congenital malformations of head & neck originate during transformation of pharyngeal apparatus
into adult derivatives
 Pharyngeal arches – develop early in the 4th week & appear as obliquely disposed, rounded ridges on
each side of future head & neck region
o By end of 4th week, well-defined pairs of branchial arches are visible externally
o The 5th & 6th arches are rudimentary
o Arches are separated by prominent branchial grooves (numbered in a craniocaudal sequence)
 1st arch: mandibular arch – develops from 2 prominences: mandibular process (lower
jaw) & maxillary process (upper jaw)
 2nd arch: hyoid arch – contributes to hyoid bone & adjacent regions of neck
o Arches support the lateral walls of cranial part of foregut (primitive pharynx)
o Mouth initially appears as a slight depression of the surface ectoderm – stomodeum
 Initially separated from primitive pharynx by buccopharyngeal membrane
 Composed of ectoderm externally & endoderm internally
 Ruptures ~day 24 – brings GI tract into communication w/ amniotic cavity
o Each arch has a mesodermal core & is covered externally by ectoderm & internally by
endoderm
o Neural crest cells derived from neuroectoderm migrate into branchial arches from neural crest &
surround mesoderm of each arch
 Mesoderm gives rise to the muscles derived from the arches
 Neural crest cells give rise to the skeletal & connective tissue of lower face & anterior
region of neck
o Each arch contains an artery, cartilaginous bar, a muscle element, & a nerve
o 1st arch is involved w/ development of the face
 Small elevations develop @ dorsal ends of 1st & 2nd arches surrounding the 1st groove
 Gradually fuse to form the external ear (auricle)
o 2nd arch overgrows the 3rd & 4th arches forming an ectodermal depression – cervical sinus
  Gradually the 2nd – 4th grooves & cervical sinus are obliterated
 Gives the neck a smooth contour
o Arches caudal to 1st arch make little contribution to the skin of the head & neck
o 1st arch: dorsal end of Meckel’s cartilage closely related to developing ear & becomes ossified to
form malleus & incus
 Intermediate portion of cartilage regresses & its perichondrium forms the anterior
ligament of the malleus & the sphenomandibular ligament
 Ventral portion of 1st arch cartilage (Meckel’s cartilage) largely disappears & mandible
develops around it by intramembranous ossification
 Muscles of mastication derived from 1st arch
 Trigeminal nerve (CN V)
o 2nd arch: dorsal end of Reichert’s cartilage closely related to middle ear & ossifies to form the
stapes of middle ear & the styloid process of the temporal bone
 Portion of cartilage b/w styloid process & hyoid bone regresses & its perichondrium
forms the stylohyoid ligament
 Ventral end of 2nd arch cartilage ossifies to form lesser cornu & upper part of the body of
the hyoid bone
 Muscles of facial expression derived from 2nd arch
 Facial nerve (CN VII)
o 3rd arch: cartilage located in the ventral portion of the arch ossifies to form the greater cornu &
lower part of the body of the hyoid bone
 Stylopharyngeus muscle derived from 3rd arch
 Glossopharyngeal nerve (CN IX)
o 4th & 6th arches: fuse to form laryngeal cartilages except for the epiglottis
 Cartilage of epiglottis develops from mesenchyme from hypobranchial eminence
(derivative of 3rd & 4th arches)
 Pharyngeal & laryngeal muscles derived from 4th & 6th arches
 Vagus nerve branches (CN X)
 Pharyngeal Pouches – endoderm of pharynx lines inner aspect of arches & passes into pouches
o Pairs of pouches develop in craniocaudal sequence b/w arches
o 4 well-defined pairs of pouches (5th absent/rudimentary)
o Endoderm of pouches contacts ectoderm of grooves – together they form thin double-layered
membranes that separate the pouches & grooves
o 1st pouch: expands into tubotympanic recess & envelops middle ear bones
 Expanded distal portion of recess contacts 1st groove (primitive external acoustic
meatus)
 Tubotympanic recess gives rise to tympanic cavity; connection w/ pharynx gradually
elongates to form auditory tube
o 2 pouch: largely obliterated as the palatine tonsils develop; remains are tonsillar fossa
nd

 Endoderm proliferates & forms buds that grow into surrounding mesenchyme
 Buds break down & form tonsillar crypts
 Pouch endoderm forms surface epithelium & the lining of the crypts of the
palatine tonsil
 Mesenchyme surrounding crypts differentiates into lymphoid tissue & becomes
organized into lymph nodules
o 3rd pouch: extends into a solid dorsal bulbar portion & hollow ventral part
 Connection w/ pharynx reduces to narrow duct & soon degenerates
 Epithelium of each dorsal bulbar portion proliferates into the inferior parathyroid gland
 Epithelium of ventral portion proliferates, obliterating their cavities
 The 2 primordia of the thymus gland meet & fuse to form the thymus
 The thymus & parathyroid gland eventually lose contact w/ pharynx & migrate caudally
 Parathyroid glands separate from thymus & come to lie on dorsal surface of thyroid
gland (which has descended from foramen cecum of the tongue at this point)
o 4 pouch: expands into a dorsal bulbar portion & a ventral part
th

 Connection w/ pharynx becomes reduced to narrow duct that soon degenerates

  Each dorsal portion develops into a superior parathyroid gland which comes to lie on the
dorsal surface of the thyroid gland
 Ventral part develops in an ultimobranchial body – fuses w/ thyroid gland, disseminates
to give rise to C cells of thyroid gland
 C cells differentiate from neural crest cells that migrate into caudal branchial
arches
o Thyroid – as embryo elongates & tongue grows, developing thyroid descends in front of neck
 Connected to tongue by thyroglossal duct; opening in the tongue = foramen cecum
o Tongue – median tongue bud forms in floor of pharynx just cranial to foramen cecum
 2 oval lateral lingual swellings develop
 Forms from proliferation of mesenchyme in ventromedial parts of 1st arch
 Lateral lingual swellings increase in size & merge
 Forms anterior 2/3 of tongue
 Plane of fusion = medial sulcus
 Posterior 1/3 of tongue indicated by 2 elevations caudal to foramen cecum; develops
from cranial part of hypobranchial eminence
 Line of fusion of anterior & posterior parts indicated by terminal sulcus
 Face – the 5 facial primordia appear around stomodeum early in 4th week
o 1) unpaired frontonasal prominence = upper boundary of stomodeum; results from proliferation
of mesenchyme ventral to developing brain
o 2) paired maxillary prominences of 1st arch = lateral boundaries of stomodeum
o 3) paired mandibular prominences of 1st arch = lower boundary of stomodeum
o By end of 4th week bilateral thickenings of surface ectoderm develop on side of frontonasal
prominence – nasal placodes
 Mesenchyme proliferates at margins of placodes producing mesial & lateral nasal
prominences
 Nasal placodes now lie in nasal pits
o Maxillary prominences grow & approach each other & the medial nasal prominences
 Each lateral nasal prominence is separated from maxillary prominences by nasolacrimal
groove
o During 6th & 7th weeks, medial nasal prominences merge w/ each other & maxillary prominences
 As medial nasal prominences merge w/ each other, intermaxillary segment of upper jaw
is formed
 Gives rise to philtrum of lip, middle portion of upper jaw & associated gingiva, &
the primary palate
 Lateral parts of the upper lip, upper jaw, & secondary palate form from maxillary
prominences
 Maxillary prominences merge laterally w/ mandibular prominences (reducing size
of mouth)
 Primitive lips & cheeks are invaded by 2nd arch mesenchyme – gives rise to facial
muscles
o Frontonasal prominence forms forehead & dorsum & apex of nose
 Sides of nose derived from lateral nasal prominences
o Mandibular prominences merge w/ each other in 4th week & groove b/w them disappears before
end of 5th week
 Gives rise to lower jaw, lower lip, & lower part of face
 Palate – develops from primary & secondary palates; development begins during 5th week, but fusion
not complete until 12th week
o Primary palate = median palatine process; develops from innermost part of intermaxillary
segment of upper jaw
o Secondary palate = lateral palatine process; develops from 2 horizontal mesodermal projections
from inner surfaces of maxillary prominences
 As jaw forms, tongue moves downward & lateral palatine processes grow toward each
other & fuse
 Also fuse w/ primary palate & nasal septum (developed from downgrowth from
merged medial nasal prominences)
  Fusion begins anteriorly during 9th week
 Membrane bone develops in primary palate & forms premaxillary part of upper jaw
 Bone extends from the maxillae & palatine bones into lateral palatine processes to form
hard palate
 Posterior portions of lateral palatine processes don’t become ossified – extends
beyond nasal septum & fuse to form soft palate & uvula
 Uvula is last part of palate to form
o Palatine raphe indicated line of fusion of lateral palatine processes
 Nasal cavities – each nasal sac grows dorsocaudally ventral to developing brain
o Initially separated from oral cavity by oronasal membrane
 Soon ruptures & brings nasal & oral cavities into communication
o After the secondary palate develops, choanae are at jxn of nasal cavity & pharynx
o When lateral palatine processes fuse w/ each other & nasal septum, the oral & nasal cavities
are again separated
 Fusion also results in separation of nasal cavities from each other
o Conchae develop as elevations on lateral wall of each nasal cavity
Cleft Lip & Palate:
 Cleft lip – malformation of upper lip; more frequent in males; may be unilateral or bilateral
o Unilateral cleft lip: failure of maxillary prominence on affected side to merge w/ merged medial
nasal prominences
 Failure of mesenchymal masses to merge & the mesenchyme to proliferate & push out
overlying epithelium
 Result is persistent labial groove; epithelium in labial groove becomes stretched & then
breakdown of tissues in floor of persistent groove leads to division of lip into medial &
lateral parts
o Bilateral cleft lip: failure of mesenchymal masses of maxillary prominences to meet & merge w/
merged medial nasal prominences
 Epithelium in both labial grooves becomes stretched & breaks down
 In complete bilateral cleft of upper lip & alveolar process, intermaxillary segment hangs
free & projects anteriorly
 Loss of continuity of orbicularis oris muscle
 Cleft palate – failure of mesenchymal masses of lateral palatine processes to meet & fuse w/ each
other, w/ nasal septum, &/or w/ posterior margin of median palatine process or primary palate
o Can be unilateral or bilateral; classified in 3 groups
o Clefts of anterior or primary palate: clefts anterior to incisive foramen resulting from failure of
mesenchymal masses of lateral palatine processes to meet & fuse w/ mesenchyme of primary
palate
o Clefts of anterior & posterior palate: clefts involving both the primary & secondary palate; results
from failure of mesenchymal masses of lateral palatine processes to meet & fuse w/
mesenchyme of primary palate, each other, & the nasal septum
o Clefts of posterior or secondary palate: clefts posterior to incisive foramen resulting from failure
of mesenchymal masses of lateral palatine processes to meet & fuse w/ each other & the nasal
septum
o Causes – genetic factors more important than environmental in cleft lip w/ or w/o cleft palate
than in cleft palate alone; mainly caused by mutant genes
 Microstomia – results from excessive merging of mesenchymal masses of maxillary & mandibular
prominences of 1st arch
Articular & Skeletal Systems:
 Develop from mesoderm; each somite becomes differentiated into a ventromedial part (sclerotome) & a
dorsolateral part (dermomyotome)
o Sclerotome cells give rise to bones, cartilage, ligaments
o Dermomyotome cells give rise to skeletal muscles & dermis of skin
 Most bones first appear as condensations of mesenchymal cells which give rise to hyaline cartilage
models that become ossified by endochondral ossification
o Some bones develop in mesenchyme by intramembranous bone formation
  Intramembranous ossification = bone formation in mesenchyme; mesenchyme becomes highly
vascular; some cells differentiate into osteoblasts & deposit matrix which will calcified
 Endochondral ossification = bone formation in pre-existing cartilaginous models
 During 4th week, cells from sclerotome migrate in 3 directions
o 1) ventromedially to surround notochord; appear as condensations of mesenchymal cells along
notochord
o 2) dorsally to cover neural tube; mesenchymal cells will form vertebral/neural arch of vertebra
o 3) ventrolaterally into body wall; mesenchymal cells will form costal processes which will
develop into ribs
 Skull develops from mesenchyme around the developing brain
o Consists of neurocranium (protective case for brain) & viscerocranium (main skeleton of jaws)
o Cartilaginous neurocranium initially consists of cartilaginous base of developing skull
 Endochondral ossification of neurocranium forms bones of base of skull
o Membranous neurocranium – intramembranous ossification occurs in mesenchyme investing
the brain & forms cranial vault
o Cartilaginous viscerocranium consists of cartilaginous skeleton of 1st 2 pairs of branchial arches
 Following endochondral ossification, dorsal end of Meckel’s cartilage forms malleus &
incus, dorsal end of Reichert’s cartilage forms stapes & styloid process of temporal bone
& ventral end ossifies to form lesser cornu & upper part of body of hyoid bone
o Membranous viscerocranium – intramembranous ossification occurs w/in maxillary process of
1st branchial arch & forms maxilla, zygomatic, & squamous temporal bones
 Squamous temporal bones later become part of neurocranium
 Mesenchyme of mandibular process condenses around Meckel’s cartilage & undergoes
intramembranous ossification to form mandible
 *Meckel’s cartilage doesn’t form adult mandible
Muscular System:
 Myoblast that form skeletal musculature are derived from mesenchyme from myotome regions of
dermomyotome parts of somites
o Mesenchyme in branchial arches & from somatic mesoderm also gives rise to skeletal muscle
 Migration of myoblasts from branchial arches forms muscles of mastication, facial expression, pharynx,
& larynx
 Musculature of limbs developed from mesenchyme surrounding developing bones
o Mesenchyme derived from somatic layer of lateral plate mesoderm
Limb Development:
 Limb buds first appear as small elevations of ventrolateral body wall toward end of 4th week
 Arm buds develop opposite the caudal cervical segments
o Each limb bud consists of mass of mesenchyme derived from somatic mesoderm & is covered
by a layer of ectoderm
o Apical ectodermal ridge exerts inductive influence on mesenchyme which promotes growth &
development of limbs
Nervous System:
 Develops from thickened area of embryonic ectoderm (neural plate) ~18 days
 Notochordal process & paraxial mesoderm act as primary inductors & determine differentiation of
embryonic ectoderm into the neural plate
o Neural tube differentiates into CNS (brain & spinal cord)
o Neural crest gives rise to most of PNS (cranial, spinal, & autonomic ganglia & nerves)
 Neural tube is temporarily open both cranially & caudally
o Cranial opening (rostral neuropore) closes ~24 days
o Caudal neuropore closes ~26 days
o Walls of neural tube thicken to form brain & spinal cord
 Unipolar neurons in dorsal root ganglia are derived from neural crest cells
 Pituitary gland develops from ectoderm of primitive mouth cavity & neuroectoderm of diencephalon
Special Sense Organs:
 Eyes – develop from neuroectoderm, surface ectoderm, & mesoderm
o First evident ~22 days when optic grooves appear in neural folds at cranial end of embryo
 o Grooves evaginate to form optic vesicles (project from sides of forebrain into adjacent
mesenchyme)
 Formation of optic vesicles induced by mesenchyme that lies adjacent to developing
brain
o Surface ectoderm adjacent to optic vesicles thickens & forms lens placodes (induced by optic
vesicles)
o Eyelids develop from 2 ectodermal folds that have cores of mesenchyme
 Eyelids meet & fuse ~10th week
 Ears
o Internal ear 1st of 3 divisions of ear to appear
 Early in 4th week, thickened plate of surface ectoderm (otic placode) appears on each
side of developing hindbrain
 Placodes invaginate & sink below surface ectoderm into underlying mesenchyme to form
otic pit
o Middle ear
 Distal portion of tubotympanic recess of 1st pouch expands & becomes tympanic cavity
 Proximal unexpanded portion becomes auditory tube
 As tympanic cavity expands, endodermal epithelium gradually envelops middle ear
bones, tendons, ligaments, & chorda tympani
o External ear
 External acoustic meatus develops from dorsal end of first branchial groove
 Early tympanic membrane represented by 1st branchial membrane
 Auricle develops from auricular hillocks which develop around margins of 1st branchial
groove
 Produced by proliferation of mesenchyme from 1st & 2nd arches
Teeth:
 Develop from ectoderm & mesoderm
 Enamel derived from ectoderm of oral cavity
o All other tissues differentiate from associated mesenchyme
 Tooth development is continuous but divided into bud, cap, & bell stages
o First tooth buds appear in anterior mandibular region
 Bud stage – first indication ~6th week
o Appear as thickenings of oral epithelium (derivative of surface ectoderm)
o Localized proliferations of cells in dental laminae produce round/oval swellings = tooth buds
 Grow into mesenchyme & develop into deciduous teeth
 Tooth buds for permanent teeth w/ deciduous predecessors begin to appear ~10th week
from deeper continuations of dental lamina
 Cap stage
o Deep surface of each ectodermal tooth bud soon becomes slightly invaginated by mass of
condensed mesenchyme (dental papilla)
 Mesenchyme of dental papilla gives rise to dentin & dental pulp
o Ectodermal portion of cap-shaped developing tooth called enamel organ b/c it later produces
enamel
 Outer cellular layer of enamel organ = outer enamel epithelium
 Inner cellular layer lining the cap = inner enamel epithelium
 Central core of loosely arranged cells b/w layers of enamel epithelium = stellate
reticulum
o As enamel organ & dental papilla form, mesenchyme surrounding them condenses & forms
capsule-like structure (dental sac)
 Gives rise to cementum & periodontal ligament
 Bell stage
o As invagination of enamel organ continues, developing tooth assumes bell shape
o Mesenchymal cells in dental papilla adjacent to inner enamel epithelium differentiate into
odontoblasts
 Produce predentin & deposit it adjacent to inner enamel epithelium
 Predentin later calcifies & becomes dentin
  As dentin thickens, odontoblasts regress toward center of dental papilla but the
cytoplasmic process of odontoblasts (Tomes’ dentinal fibers/processes) remain
embedded in dentin
o Cells of inner enamel epithelium adjacent to dentin differentiate into ameloblasts
 Produce enamel in form of prisms (rods) over dentin
 As enamel increases, ameloblasts regress toward outer enamel epithelium
o Enamel & dentin formation begins at the tip (cusp) of the tooth & progresses toward the future
root
o Development of root begins after dentin & enamel formation are well advanced
 Inner & outer enamel epithelium come together in neck region of tooth & form epithelial
fold (epithelial root sheath)
 Sheath grows into mesenchyme & initiates root formation
 Odontoblasts adjacent to sheath form dentin continuous w/ that of crown
 As dentin increases, it reduces pulp cavity to narrow canal through which vessels
& nerves pass
o Inner cells of dental sac differentiate into cementoblasts which produce cementum
 Deposited over dentin of root & meets enamel at neck of tooth (cementoenamel junction)
o As teeth develop & jaws ossify, outer cells of dental sac become active in bone formation
 Each tooth becomes surrounded by bone except over crown
 Tooth held in place in periodontal ligament (derivative of dental sac)
 Some parts of ligament are embedded in cementum, other parts embedded in
bony wall of socket
 As root of tooth grows, crown gradually erupts through oral mucosa
o The part of oral mucosa around erupted crown becomes gingiva
o Eruption of deciduous teeth usually occurs b/w 6-24 months after birth
o As permanent tooth grows, root of deciduous tooth is gradually resorbed by osteoclasts
 Abnormalities not visible at birth
o Enamel hypoplasia = defective enamel formation resulting in grooves, pits, or fissures on
enamel surface
 Result from temporary disturbance in enamel formation
o Amelogenesis imperfecta = soft & friable enamel due to hypocalcification & teeth are
brown/yellow in color