NOTCH, a new signaling pathway implicated in holoprosencephaly

被引：41

作者：

Dupe, Valerie ^{[1
]}

Rochard, Lucie ^{[1
]}

Mercier, Sandra ^{[1
]}

Le Petillon, Yann ^{[1
]}

Gicquel, Isabelle ^{[1
]}

Bendavid, Claude ^{[1
,2
]}

Bourrouillou, Georges ^{[7
]}

Kini, Usha ^{[4
]}

Thauvin-Robinet, Christel ^{[5
]}

Bohan, Timothy P. ^{[6
]}

Odent, Sylvie ^{[1
,3
]}

Dubourg, Christele ^{[1
,2
]}

David, Veronique ^{[1
,2
]}

机构：

[1] Univ Rennes 1, CNRS, UMR6061, Inst Genet & Dev,Fac Med,GFAS IFR140, F-35043 Rennes, France

[2] CHU Pontchaillou, Genet Mol Lab, Rennes, France

[3] Hop Sud, Serv Genet Clin, Rennes, France

[4] Churchill Hosp, Dept Clin Genet, Oxford OX3 7LJ, England

[5] Hop Enfants, Ctr Genet Med, Dijon, France

[6] Childrens Mem Hermann Hosp, Houston, TX USA

[7] Purpan Univ Hosp, Dept Genet, Toulouse, France

来源：

HUMAN MOLECULAR GENETICS | 2011年 / 20卷 / 06期

关键词：

GROWTH-FACTOR RECEPTOR; MOLECULAR CHARACTERIZATION; EXPRESSION PATTERNS; GENE-EXPRESSION; FOREBRAIN; MUTATION; DELETIONS; FGF8; SIX3; IDENTIFICATION;

D O I：

10.1093/hmg/ddq556

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1122 / 1131

页数：10

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