NOTCH, a new signaling pathway implicated in holoprosencephaly.
Hum Mol Genet
; 20(6): 1122-31, 2011 Mar 15.
Article
in En
| MEDLINE
| ID: mdl-21196490
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Holoprosencephaly
/
Receptors, Notch
Type of study:
Prognostic_studies
Limits:
Adult
/
Animals
/
Female
/
Humans
/
Male
/
Newborn
Language:
En
Journal:
Hum Mol Genet
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2011
Type:
Article
Affiliation country:
France