Feb 28, 2003

Nonneuronal expression of the GABA(A) beta3 subunit gene is required for normal palate development in mice

Developmental Biology
N HagiwaraM H Brilliant

Abstract

Cleft palate is one of the most common birth defects in humans, in which both genetic and environmental factors are involved. In mice, loss of the GABA(A) receptor beta3 subunit gene (Gabrb3) or the targeted mutagenesis of the GABA synthetic enzyme (Gad1) leads to cleft palate. These observations indicate that a GABAergic system is important in normal palate development. To determine what cell types, neuronal or nonneuronal, are critical for GABA signaling in palate development, we used the neuron-specific enolase promoter to express the beta3 subunit in Gabrb3 mutant mice. Expression of this construct was able to rescue the neurological phenotype, but not the cleft palate phenotype. Combined with the previous observation demonstrating that ubiquitous expression of the beta3 subunit rescued the cleft palate phenotype, a nonneuronal GABAergic system is implicated in palate development. Using immunohistochemistry, we detected GABA in the developing palate, initially in the nasal aspect of palatal epithelium of the vertical shelves; later in the medial edge epithelium of the horizontally oriented palatal shelves and in the epithelial seam during fusion. Based on these observations, we propose that GABA, synthesized by the palatal ...Continue Reading

  • References35
  • Citations26

References

  • References35
  • Citations26

Citations

Mentioned in this Paper

Signaling Molecule
Mice, Inbred CBA
BHLHE22 wt Allele
Immunohistochemistry
Structure of Papilla Incisiva of Mouth
Cleft Palate, Isolated
Epithelium
Promoter
Neuron Specific Enolase Measurement
Immunocytochemistry

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