tbx6l and tbx16 are redundantly required for posterior paraxial mesoderm formation during zebrafish embryogenesis

Abstract

Background T-box genes encode a large transcription factor family implicated in many aspects of development. We are focusing on two related zebrafish T-box genes, tbx6l and tbx16, that are expressed in highly overlapping patterns in embryonic paraxial mesoderm. tbx16 mutants are deficient in trunk, but not tail, somites; we explored whether presence of tail somites in tbx16 mutants was due to compensatory function provided by the tbx6l gene. Results We generated two zebrafish tbx6l mutant alleles. Loss of tbx6l has no apparent effect on embryonic development, nor does tbx6l loss enhance the phenotype of two other T-box gene mutants, ta or tbx6, or of the mesp family gene mutant, msgn1. In contrast, loss of tbx6l function dramatically enhances the paraxial mesoderm deficiency of tbx16 mutants. Conclusion These data demonstrate that tbx6l and tbx16 genes function redundantly to direct tail somite development. tbx6l single mutants develop normally because tbx16 fully compensates for loss of tbx6l function. However, tbx6l only partially compensates for loss of tbx16 function. These results resolve the question of why loss of function of tbx16 gene, which is expressed throughout the ventral and paraxial mesoderm, profoundly affects somite development in the trunk but not the tail.

Sox2 and Canonical Wnt Signaling Interact to Activate a Developmental Checkpoint Coordinating Morphogenesis with Mesoderm Fate Acquisition

“…Here, we show that lowering the level of Wnt signaling can recapitulate the mouse Tbx6 ectopic spinal cord phenotype in zebrafish tbx16 mutants. One implication of this result is that the relative amount of Wnt signaling is higher in the zebrafish tailbud compared to the mouse, which may help explain the species-specific differences between NMP development (Martin and Kimelman, 2009;Steventon et al, 2016;Attardi et al, 2018;Mallo, 2020), including the phenotypic differences of the Tbx6 mouse mutant and the tbx16 single or tbx16/tbx6l and tbx16/msgn1 double zebrafish mutants (Chapman and Papaioannou, 1998;Fior et al, 2012;Yabe and Takada, 2012;Morrow et al, 2017).…”

“…One key difference of the mouse Tbx6 mutant compared to the zebrafish tbx16 mutant is that in the mouse, a subset of cells exit the tailbud to form ectopic spinal cords where somites should normally form (Chapman and Papaioannou, 1998). Ectopic neural tissue is never observed in the zebrafish tbx16 mutant or in the tbx16/msgn1 or tbx16/tbx16l double mutants, which have a more severe phenotype than the tbx16 single mutant (Fior et al, 2012;Yabe and Takada, 2012;Morrow et al, 2017). Here, we show that lowering the level of Wnt signaling can recapitulate the mouse Tbx6 ectopic spinal cord phenotype in zebrafish tbx16 mutants.…”

Transcriptional autoregulation of zebrafish tbx6 is required for somite segmentation

“…In contrast to the single Tbx6 gene in mice, three structural tbx6 homologs (tbx6, tbx16 and tbx16l) were identified in zebrafish (Griffin et al, 1998;Hug et al, 1997;Nikaido et al, 2002). In zebrafish, tbx6 was originally isolated and named tbx24 (Nikaido et al, 2002), and tbx16l was first named as tbx6 (Hug et al, 1997) and subsequently renamed as tbx6l (Morrow et al, 2017). As medaka also possesses three tbx6-related genes, tbx6 genes in teleosts must have diverged by teleost-specific gene duplication.…”

Muscle precursor cell movements in zebrafish are dynamic and require six-family genes

“…Non-fluorescent RNA in situ hybridization was also performed using established protocols (Jowett, 1999). We mounted embryos for imaging as described previously (Morrow et al, 2017). For all in situ experiments, to prevent pigment formation, embryos were treated with 0.003% N-phenylthiourea (PTU) beginning at 24 hpf.…”