NOTCH, a new signaling pathway implicated in holoprosencephaly

作者：Dupe Valerie; Rochard Lucie; Mercier Sandra; Le Petillon Yann; Gicquel Isabelle; Bendavid Claude; Bourrouillou Georges; Kini Usha; Thauvin Robinet Christel; Bohan Timothy P; Odent Sylvie; Dubourg Christele; David Veronique^*

来源：Human Molecular Genetics, 2011, 20(6): 1122-1131.

DOI：10.1093/hmg/ddq556

Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing human forebrain, is due to multiple genetic defects. Most genes that have been implicated in HPE belong to the sonic hedgehog signaling pathway. Here we describe a new candidate gene isolated from array comparative genomic hybridization redundant 6qter deletions, DELTA Like 1 (DLL1), which is a ligand of NOTCH. We show that DLL1 is co-expressed in the developing chick forebrain with Fgf8. By treating chick embryos with a pharmacological inhibitor, we demonstrate that DLL1 interacts with FGF signaling pathway. Moreover, a mutation analysis of DLL1 in HPE patients revealed a three-nucleotide deletion. These various findings implicate DLL1 in early patterning of the forebrain and identify NOTCH as a new signaling pathway involved in HPE.

• 出版日期2011-3-15