Alternative splicing, phylogenetic analysis, and craniofacial expression of zebrafish tbx22.

Mutations in human TBX22 cause X-linked cleft palate with ankyloglossia syndrome (CPX; OMIM 303400). Since the secondary palate was an adaptation to breathing on land, we characterized zebrafish tbx22 to study molecular mechanisms regulating early vertebrate craniofacial patterning. Rapid Amplification of cDNA Ends (RACE) analyses revealed two zebrafish tbx22 splice isoforms, tbx22-1 and tbx22-2, encoding proteins of 444 and 400 amino acids, respectively. tbx22-1 resembles canonical Tbx22 orthologs, while tbx22-2 lacks conserved N-terminal sequence. Developmental RT-PCR revealed that tbx22-1 is maternally and zygotically expressed, while tbx22-2 is expressed zygotically. WISH analyses revealed strong tbx22 mRNA expression in ectomesenchyme underlying the stomodeum, a bilaminar epithelial structure demarcating early mouth formation, and in early presumptive jaw joints. Zebrafish tbx22 expression mirrored some aspects of mammalian Tbx22, consistent with roles in early vertebrate face patterning. These studies identify an early transcription factor governing vertebrate facial development, which may underlie common craniofacial birth disorders. Developmental Dynamics 238:1605-1612, 2009. (c) 2009 Wiley-Liss, Inc.

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