Specification of theC. elegansMS blastomere by the T-box factor TBX-35

Abstract

In C. elegans, many mesodermal cell types are made by descendants of the progenitor MS, born at the seven-cell stage of embryonic development. Descendants of MS contribute to body wall muscle and to the posterior half of the pharynx. We have previously shown that MS is specified by the activity of the divergent MED-1,2 GATA factors. We report that the MED-1,2 target gene tbx-35, which encodes a T-box transcription factor, specifies the MS fate. Embryos homozygous for a putative tbx-35-null mutation fail to generate MS-derived pharynx and body muscle, and instead generate ectopic PAL-1-dependent muscle and hypodermis, tissues normally made by the C blastomere. Conversely, overexpression of tbx-35 results in the generation of ectopic pharynx and muscle tissue. The MS and E sister cells are made different by transduction of a Wnt/MAPK/Src pathway signal through the nuclear effector TCF/POP-1. We show that in E, tbx-35 is repressed in a Wnt-dependent manner that does not require activity of TCF/POP-1, suggesting that an additional nuclear Wnt effector functions in E to repress MS development. Genes of the T-box family are known to function in protostomes and deuterostomes in the specification of mesodermal fates. Our results show that this role has been evolutionarily conserved in the early C. elegans embryo, and that a progenitor of multiple tissue types can be specified by a surprisingly simple gene cascade.

The NK-2 class homeodomain factor CEH-51 and the T-box factor TBX-35 have overlapping function inC. elegansmesoderm development

“…Loss of med-1,2 leads to a highly expressive loss of MS-derived tissues, whereas loss of tbx-35 has a less expressive MS phenotype, especially at lower temperatures (Broitman-Maduro et al, 2006;Maduro et al, 2001) (this work), suggesting that an additional factor contributes to MS specification downstream of MED-1,2 (Broitman- Maduro et al, 2006). From embryonic transcriptome analyses (Baugh et al, 2005;Baugh et al, 2003), we identified Y80D3A.3 as a candidate early MS lineage gene.…”

“…3I,J), in which additional MS-like cells are made from the AB and C lineages, respectively (Mello et al, 1992). We have previously found that tbx-35 is still expressed in MS in a pop-1(RNAi) background (Broitman-Maduro et al, 2006), even though in this background MS adopts an E-like fate (Lin et al, 1995). Unexpectedly, most pop-1(RNAi) embryos expressed ceh-51 in both the MS and E lineages (Fig.…”

“…By contrast, tbx-35 null mutants arrest with varying degrees of elongation, ranging from 1-fold to complete elongation and hatching (Broitman-Maduro et al, 2006 (Fig. 8P).…”

“…Loss of med-1,2 has a similar effect on MS specification as loss of skn-1, but a much weaker effect on E specification owing to parallel contributions to endoderm from SKN-1 and other factors (Goszczynski and McGhee, 2005;Maduro et al, 2005a;Maduro et al, 2001). In MS, MED-1,2 activate the T-box factor gene tbx-35 (Broitman-Maduro et al, 2006). Loss of tbx-35 has variable effects on MS lineage development and morphogenesis, although the most severely affected mutants resemble skn-1 or med-1,2 embryos and lack most tissues made by MS (Broitman- Maduro et al, 2006).…”

“…In MS, MED-1,2 activate the T-box factor gene tbx-35 (Broitman-Maduro et al, 2006). Loss of tbx-35 has variable effects on MS lineage development and morphogenesis, although the most severely affected mutants resemble skn-1 or med-1,2 embryos and lack most tissues made by MS (Broitman- Maduro et al, 2006).…”