Early expression of the <i>tbx</i>22 gene in zebrafish influences positioning of pharyngeal arch cartilages

Abstract

Mutations in human TBX 22 cause X-linked cleft palate with anklyoglossia syndrome. The two zebrafish tbx 22 splice isoforms, tbx 22-1 and tbx 22-2, encode proteins of 444 and 400 amino acids, respectively. Zebrafish tbx 22 mRNA expression mirrors mammalian TBX 22 expression and is consistent with early patterning of the vertebrate face. In zebrafish, tbx 22 mRNA is strongly expressed during early pharyngeal arch development in the ventral mesenchyme, and a later expression domain is found in ectomesenchymal cells underlying the stomodeum, a bilaminar epithelial structure demarcating the early forming mouth. Therefore, tbx 22 is hypothesized to be involved in craniofacial development. The objective of this work is to characterize the role of tbx 22 during craniofacial development in zebrafish. Tbx 22 knockdown revealed that defects in tbx 22 signaling cause mild clefting, joint defects and dorsoventral patterning defects in cartilages. Quantitative PCR and in situ analysis revealed that knockdown of tbx 22 also causes a dramatic decrease in expression of osr 1 and gdf 5. Craniofacial patterning is dependent on proper signals from endoderm, mesoderm and ectoderm. The early influence of tbx 22 on signals within the ventral mesenchyme impacts the domains of several key pharynx-geal arch signals, thereby helping to regulate proper patterning of the developing jaw.