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Heparan sulfate Ndst1 gene function variably regulates multiple signaling pathways during mouse development
Author(s) -
Pallerla Srinivas R.,
Pan Yi,
Zhang Xin,
Esko Jeffrey D.,
Grobe Kay
Publication year - 2007
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21038
Subject(s) - biology , fibroblast growth factor , neural tube , heparan sulfate , sonic hedgehog , wnt signaling pathway , hedgehog , forebrain , phenotype , microbiology and biotechnology , homeobox , mutant , hedgehog signaling pathway , zebrafish , loss function , signal transduction , genetics , medicine , endocrinology , gene , central nervous system , embryo , transcription factor , receptor , cell
Disruption of heparan sulfate (HS) synthesis in vertebrate development causes malformations that are composites of those caused by mutations of multiple HS binding growth factors and morphogens. We previously reported severe developmental defects of the forebrain and the skull in mutant mice bearing a targeted disruption of the heparan sulfate‐generating enzyme GlcNAc N‐deacetylase/GlcN N‐sulfotransferase 1 (Ndst1). Here, we further characterize the molecular mechanisms leading to frontonasal dysplasia in Ndst1 mutant embryos and describe additional malformations, including impaired spinal and cranial neural tube fusion and skeletal abnormalities. Of the numerous proteins that bind HS, we show that impaired fibroblast growth factor, Hedgehog, and Wnt function may contribute to some of these phenotypes. Our findings, therefore, suggest that defects in HS synthesis may contribute to multifactor types of congenital developmental defects in humans, including neural tube defects. Developmental Dynamics 236:556–563, 2007. © 2006 Wiley‐Liss, Inc.