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


Authors: Zohn, I. E.; Anderson, K. V.; Niswander, L.
Article Title: 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. © 2007 Elsevier Inc. All rights reserved.
Keywords: controlled study; protein expression; gene mutation; mutation; nonhuman; protein domain; biological markers; animal cell; mouse; animals; mice; allele; animal tissue; gene; gene expression; ubiquitin protein ligase; embryo; animal experiment; animal model; mice, mutant strains; alleles; embryo development; gene function; heterozygote; wild type; central nervous system; animalia; molecular marker; brain development; genetic susceptibility; nucleotide sequence; protein structure, tertiary; neural crest; mesoderm; ubiquitin-protein ligases; ethylnitrosourea; mesenchyme; neural tube; embryonic development; mutant; penetrance; neural tube defect; ubiquitin ligase; skull; neural tube closure; neural tube defects; exencephaly; enu mutagenesis; head mesenchyme; hectd1 gene
Journal Title: Developmental Biology
Volume: 306
Issue: 1
ISSN: 0012-1606
Publisher: Elsevier Inc.  
Date Published: 2007-06-01
Start Page: 208
End Page: 221
Language: English
DOI: 10.1016/j.ydbio.2007.03.018
PUBMED: 17442300
PROVIDER: scopus
PMCID: PMC2730518
DOI/URL:
Notes: --- - "Cited By (since 1996): 9" - "Export Date: 17 November 2011" - "CODEN: DEBIA" - "Molecular Sequence Numbers: GENBANK: AAP13073;" - "Source: Scopus"
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  1. Kathryn Anderson
    141 Anderson