Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development.
Little is known about the mechanism by which embryonic liver, lung, and pancreas progenitor cells emerge from the endodermal epithelium to initiate organogenesis. Understanding this process and its genetic control provides insight into ontogeny, developmental abnormalities, and tissue regeneration. We find that shortly after hepatic endoderm cells are specified, they undergo a transition from a columnar, gut morphology to a pseudostratified morphology, with concomitant "interkinetic nuclear migration" (INM) during cell division. INM is a hallmark of pseudostratified epithelia and the process used by neural progenitors to emerge from the neural epithelium. We find that the transition of the hepatic endoderm, but not the neural epithelium, to a pseudostratified epithelium is dependent upon the cell-autonomous activity of the homeobox gene Hex. In the absence of Hex, hepatic endoderm cells survive but maintain a columnar, simple epithelial phenotype and ectopically express Shh and other genes characteristic of the midgut epithelium. Thus, Hex promotes endoderm organogenesis by promoting the transition to a pseudostratified epithelium, which in turn allows hepatoblasts to emerge into the stromal environment and continue differentiating.
Bort
Roque
R
Cell and Developmental Biology Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Signore
Massimo
M
Tremblay
Kimberly
K
Martinez Barbera
Juan Pedro
JP
Zaret
Kenneth S
KS
D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D004707:Endoderm / Q000166:cytology* / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000196:embryology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D038081:Organogenesis; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D053823:Hedgehog Proteins; C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors