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The Hectd1 ubiquitin ligase is required for development of the head mesenchyme and neural tube closure.

Abstract：

:Closure of the cranial neural tube depends on normal development of the head mesenchyme. Homozygous-mutant embryos for the ENU-induced open mind (opm) mutation exhibit exencephaly associated with defects in head mesenchyme development and dorsal-lateral hinge point formation. The head mesenchyme in opm mutant embryos is denser than in wildtype embryos and displays an abnormal cellular organization. Since cells that originate from both the cephalic paraxial mesoderm and the neural crest populate the head mesenchyme, we explored the origin of the abnormal head mesenchyme. opm mutant embryos show apparently normal development of neural crest-derived structures. Furthermore, the abnormal head mesenchyme in opm mutant embryos is not derived from the neural crest, but instead expresses molecular markers of cephalic mesoderm. We also report the identification of the opm mutation in the ubiquitously expressed Hectd1 E3 ubiquitin ligase. Two different Hectd1 alleles cause incompletely penetrant neural tube defects in heterozygous animals, indicating that Hectd1 function is required at a critical threshold for neural tube closure. This low penetrance of neural tube defects in embryos heterozygous for Hectd1 mutations suggests that Hectd1 should be considered as candidate susceptibility gene in human neural tube defects.

journal_name

Dev Biol

journal_title

Developmental biology

authors

Zohn IE,Anderson KV,Niswander L

doi

10.1016/j.ydbio.2007.03.018

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

208-21

issue

1

eissn

0012-1606

issn

1095-564X

pii

S0012-1606(07)00219-9

journal_volume

306

pub_type

杂志文章

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