Cleft Palate Is Caused by CNS Dysfunction in Gad1 and Viaat Knockout MiceReport as inadecuate




Cleft Palate Is Caused by CNS Dysfunction in Gad1 and Viaat Knockout Mice - Download this document for free, or read online. Document in PDF available to download.

Background

Previous studies have shown that disruption of GABA signaling in mice via mutations in the Gad1, Gabrb3 or Viaat genes leads to the development of non-neural developmental defects such as cleft palate. Studies of the Gabrb3 and Gad1 mutant mice have suggested that GABA function could be required either in the central nervous system or in the palate itself for normal palatogenesis.

Methodology-Principal Findings

To further examine the role of GABA signaling in palatogenesis we used three independent experimental approaches to test whether Gad1 or Viaat function is required in the fetal CNS for normal palate development. We used oral explant cultures to demonstrate that the Gad1 and Viaat mutant palates were able to undergo palatogenesis in culture, suggesting that there is no defect in the palate tissue itself in these mice. In a second series of experiments we found that the GABAA receptor agonist muscimol could rescue the cleft palate phenotype in Gad1 and Viaat mutant embryos. This suggested that normal multimeric GABAA receptors in the CNS were necessary for normal palatogenesis. In addition, we showed that CNS-specific inactivation of Gad1 was sufficient to disrupt palate development.

Conclusions-Significance

Our results are consistent with a role for Gad1 and Viaat in the central nervous system for normal development of the palate. We suggest that the alterations in GABA signaling lead to non-neural defects such as cleft palate as a secondary effect due to alterations in or elimination of fetal movements.



Author: Won-Jong Oh, Joby J. Westmoreland, Ryan Summers, Brian G. Condie

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents