Heterozygous loss-of-function mutations in SHH cause holoprosencephaly (MIM: 142945) and studies in both mouse and human embryos have shown that SHH expression needs to be repressed in the dorsal foregut endoderm for successful differentiation toward dorsal pancreas.6, 10 A recent study has suggested that the transcription factors Gata4 and Gata6 (mutations in which are a cause of pancreatic agenesis) regulate pancreatic endoderm identity by directly inhibiting Shh in mice.11 Here, SHH is linked to holoprosencephaly.