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

Developmental biology | 2007

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.

Pubmed ID: 17442300 RIS Download

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Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: U01 HD043478
  • Agency: NICHD NIH HHS, United States
    Id: U01-HD43478
  • Agency: NICHD NIH HHS, United States
    Id: F32 HD008605
  • Agency: NICHD NIH HHS, United States
    Id: U01 HD043478-05
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD035455-05
  • Agency: NICHD NIH HHS, United States
    Id: F32 HD008605-04
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD035455
  • Agency: NICHD NIH HHS, United States
    Id: F32-HD08605
  • Agency: NICHD NIH HHS, United States
    Id: R01-HD035455

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BayGenomics (tool)

RRID:SCR_008168

THIS RESOURCE IS NO LONGER IN SERVICE, documented August 29, 2016. The BayGenomics gene-trap resource provides researchers with access to thousands of mouse embryonic stem (ES) cell lines harboring characterized insertional mutations in both known and novel genes. The major goal of BayGenomics is to identify genes relevant to cardiovascular and pulmonary disease.

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