Notochord repression of endodermal Sonic hedgehog permits pancreas development.
Notochord signals to the endoderm are required for development of the chick dorsal pancreas. Sonic hedgehog (SHH) is normally absent from pancreatic endoderm, and we provide evidence that notochord, in contrast to its effects on adjacent neuroectoderm where SHH expression is induced, represses SHH expression in adjacent nascent pancreatic endoderm. We identify activin-betaB and FGF2 as notochord factors that can repress endodermal SHH and thereby permit expression of pancreas genes including Pdx1 and insulin. Endoderm treatment with antibodies that block hedgehog activity also results in pancreatic gene expression. Prevention of SHH expression in prepancreatic dorsal endoderm by intercellular signals, like activin and FGF, may be critical for permitting early steps of chick pancreatic development.
Hebrok
M
M
Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138 USA.
Kim
S K
SK
Melton
D A
DA
D028341:Activins; D000818:Animals; D002642:Chick Embryo; D004627:Embryonic Induction; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D009842:Oligopeptides; D010179:Pancreas / Q000196:embryology* / Q000502:physiology*; D010455:Peptides / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D015534:Trans-Activators
D053823:Hedgehog Proteins; D009842:Oligopeptides; D010455:Peptides; D011506:Proteins; D015534:Trans-Activators; C044147:activin B; D028341:Activins; C048617:myelopeptides