name two factors involved in differentiating vetnral endoderm into liver lineages
FGF-from the cardiac mesoderm BMP- from the septum transversum mesenchyme cells -induce liver program and suppress the pancreas program
what are two transcription factors that help regionalize the gut?
Pdx1 and Hex--DNA binding proteins that activate transcriptional programs, regionalized patterns of expression in different parts of the digestive system
how might you show that Hex expression marks the birth of the liver?
hepatoblasts are stained blue by marking Hex, you can look at different time points to see the stages of liver bud organogenesis, Hex expression correlates to the budding/birth of the liver, can see it move out and develop
What is Pdx1?
Pdx1 marks the birth of the pancreas, transcription factor -a homeodomain protein expressed in the pancreas and required for pancreatic development
What is so weird about pancreatic budding?
the liver and pancreas primordia both bud from the gut, but the pancreas buds in two distinct places through different means, the dorsal and ventral pancreatic lobes develop independently the fuse together to create one functional organ
how are similar endoderm primoridal specified?
signals from the heart promote some tissue to become the liver and blocks it in other tissue (this will become the pancreas) paracrine signaling: notochord blocks hepatogensis, cardiogenic mesoderm also blocks this same part of the endoderm, it promotes the hepatic region of the gut endoderm expressing alpha-fetal protein and albumin
what is the point of FGF signaling in the cardiogenic mesoderm?
FGF signaling from cardiogenic mesoderm induces liver development and blocks pancreatic development fibroblast growth factor, paracrine signaling molecule, released from one cell and stimulates the cells nearby to differentiate into specific tissues, makes cells in the endoderm become liver
describe the factors involved in differentiating ventral endoderm into hepatoblasts or pancreatic progenitors
BMP-bone marphagenic protein, along with FGF it helps specific tissue to be instructed to become the liver and ventral pancreatic endoderm (by blocking liver development there) -FGF and BMP tells tissue to express hex, which causes hepatoblasts -pdx1 leads to pancreatic prognitors
what drives dorsal endoderm to pancreatic progenitors?
dorsal posterior endoderm is supressed by Shh from notochrod and activated by activin/TGFbeta leading to pancreatic progintors
describe compensatory regneration
proliferation of existing differentiated cells to replace lost cells -liver regeneration by hepatocyte replication--requires multiple cell types and signaling pathways; kupffer (specialized WBC) turn on proliferation, hepatocytes will replicate until they make up the cells that were lost--this is not mediated by stem cells, no stem cell pool in those organs -modest pancreatic response to injury
what is some evidence that tissue specific stem cells are in a similar state to their embryonic rudiment?
sox2: trancription factor requried for embryonic neuroepithelial development and postnatal neuronal stem cells runx1: trancription factor requried for embryonic initiation of hematopoietic tissue and postnatal HSCs
what is evidence for an alternate hypothesis?
postnatal appearance of non-embryonic nestin positive pituitary stem cell
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