tbx5 and tbx15 mediate zebrafish posterior lateral line migration and development via a negative feedback loop

Abstract

The zebrafish posterior lateral line (pLL) is a mechanosensory organ enabling detection of movement in the aqueous environment. Evidence suggests that two T-box transcription factors, tbx5 and tbx15, participate in pLL migration and development. Lateral line migration and deposition defects are observed following tbx5 or tbx15 morpholino knockdown. Additional studies demonstrate that the tbx5 phenotype is partially rescued when tbx15 is also knocked down. pLL defects similar to those of tbx5 are noted following knockdown of camKII-{beta}2, a known downstream target of Tbx5, suggesting a potential mechanistic pathway. Ectopic expression of human CamKII-{partial}C partially rescues the tbx5 phenotype but exacerbates the tbx15 phenotype. These results, combined with in situ hybridization and qRT-PCR profiling, indicate a negative feedback loop controlling multiple primordium patterning markers, including cxcr4b, cxcr7b, fgf10a and notch3, which ultimately affects pLL neuromast migration and deposition.