Notochord repression of endodermal Sonic hedgehog permits pancreas development

M Hebrok, SK Kim, DA Melton - Genes & development, 1998 - genesdev.cshlp.org
M Hebrok, SK Kim, DA Melton
Genes & development, 1998genesdev.cshlp.org
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-βB and FGF2 as notochord factors that can repress
endodermal SHH and thereby permit expression of pancreas genes including Pdx1 and …
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-βB 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.
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