Nonneuronal expression of the GABAA β3 subunit gene is required for normal palate development in mice

Nobuko Hagiwara, Zoya Katarova, Linda D. Siracusa, Murray H. Brilliant

Research output: Contribution to journalArticle

41 Scopus citations

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 GABAA receptor β3 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 β3 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 β3 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 epithelium, acts as a signaling molecule during orientation and fusion of the palate shelves.

Original languageEnglish (US)
Pages (from-to)93-101
Number of pages9
JournalDevelopmental Biology
Volume254
Issue number1
DOIs
StatePublished - Feb 1 2003

Keywords

  • Cleft palate
  • GABA
  • GABA β3 subunit
  • Palate development

ASJC Scopus subject areas

  • Developmental Biology

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