Notochord repression of endodermal Sonic hedgehog permits pancreas development

TLDR

Notochord signals to endoderm are required for chick dorsal pancreas development. The authors demonstrate that notochord‑derived activin‑βB and FGF2 repress endodermal SHH, permitting pancreatic gene expression, and that hedgehog inhibition likewise induces pancreatic genes, underscoring SHH repression as critical for early pancreas development.

Abstract

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.