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For Liver Bud development [Point to liver bud development part in photo.], the cardiogenic mesoderm secretes growth factors
FGF1 and FGF2 that will create a gradient. Signaling of FGF and another protein called BMP (Bone Morphogenic protein)
directs hepatogenesis and triggers liver bud development into the septum transversum. Another protein called HHEX
(hematopoiecally-expressed homeobox protein) also regulates the proliferation, position and formation of the liver bud.
Furthermore, Liver stem cells, called Hepatoblasts are later become hepatocytes of the mature liver or cholangiocytes of bile
ducts.
[Point to next photo of liver bud growth]
For Liver development, the liver bud hepatoblasts must replicate. Signals, called homeobox-like protein (Hlx) and Hepatocyte
Growth Factor (HGF), are expressed from the Septum Transversum and cause liver this growth.
[Point to next photo of developed liver]
Once the liver bud is formed, Wnt2/-catenin signalling affects morphology by regulating lobule formation. -catenin is a
protein normally in the cytoplasm. Once Wnt binds to its receptor, B-catenin is released and translocates to the nucleus. This
increases hepatocyte expansion and maturation by increasing cell-cell adhesion.
Pancreas originates from the duodenum as a dorsal bud and a ventral bud. These buds expand and move towards each other
until they fuse.
The formation of pancreatic bud formation requires the suppression of Shh in the endoderm. The application of the Shh
inhibitor, cyclopamine, to the endoderm will provoke the formation of pancreatic buds from the zone expressing Pdx1. Pdx1 is
expressed in all cells of the early buds and is necessary for their formation. Another necessary gene is Hlxb9, which encodes
homeodomain, Hb9. This protein is expressed in a wider region than Pdx1 and at an even earlier stage.
Next, PTF1 is a three subunit transcription factor required to upregulate various exocrine genes.
In the outgrowth of buds, the DORSAL BUD of the pancreas appears in a region where the notochord contacts the gut roof
while VENTRAL BUD is formed from the adjacent region of the endoderm to the liver.
FGF is a protein necessary for continued growth of the buds. Specifically, FGF10 is an important mesenchymal factor in
stimulating proliferation of the pancreatic endoderm. The upshot of the Dorsal pancreatic bud is induced by FGF while the
ventral bud develops from the absence of FGF.
Neurogenin 3 (Ngn3) is key transcription factor for promoting endocrine differentiation. It is controlled by the Notch signaling
Pathway. When Notch is active, NGN3 [point at NGN3 with arrow going down] is not expressed no islets are produced.
However, when Notch is inhibited, NGN3 [point at NGN3 with arrow going up] is expressed and endocrine differentiation can
commence.