Wnt Signaling and a Hox Protein Cooperatively Regulate PSA-3/Meis to Determine Daughter Cell Fate after Asymmetric Cell Division in C. elegans

Abstract

Asymmetric cell division is a mechanism for achieving cellular diversity. In C. elegans, many asymmetric cell divisions are controlled by the Wnt-MAPK pathway through POP-1/TCF. It is poorly understood, however, how POP-1 determines the specific fates of daughter cells. We found that nob-1/Hox, ceh-20/Pbx, and a Meis-related gene, psa-3, are required for asymmetric division of the T hypodermal cell. psa-3 expression was asymmetric between the T cell daughters, and it was regulated by POP-1 through a POP-1 binding site in the psa-3 gene. psa-3 expression was also regulated by NOB-1 and CEH-20 through a NOB-1 binding sequence in a psa-3 intron. PSA-3 can bind CEH-20 and function after the T cell division to promote the proper fate of the daughter cell. These results indicate that cooperation between Wnt signaling and a Hox protein functions to determine the specific fate of a daughter cell.

Sustained in vitro trigger of self-renewal divisions in Hoxb4hiPbx1lo hematopoietic stem cells

“…Part of the answer may reside in proper chromatin configuration, integration of specific proliferation, differentiation, senescence or apoptosis signals, as well as intracellular segregation of key regulator molecules. Nonetheless, a role for homeotic genes in cell fate decisions is indisputable, and perturbations in the C. elegans hox-meis-pbx complex were recently shown to alter the outcome of cellular division [46]. Data from foetal stromal cells and tissue stem cell profiling may continue to provide interesting candidates.…”

-Catenin-Dependent Wnt Signaling in C. elegans: Teaching an Old Dog a New Trick

“…Conversely, in the Wntactivated daughter cell, the lower POP-1/TCF levels and higher SYS-1/b-catenin levels result in formation of a typical TCF/b-catenin bipartite transcription activator, which activates expression of target genes (Fig. 4B, right) (Calvo et al 2001;Zhao et al 2002;Maduro et al 2005;Shetty et al 2005;Arata et al 2006;Lam et al 2006;Huang et al 2007;Owraghi et al 2010). Molecular genetic manipulations that artificially alter the ratio of TCF to b-catenin between daughter cells lead to changes in gene expression or cell fate that are consistent with this model of Wnt pathway activation, switching the transcriptional behavior of TCF in the nucleus (Kidd et al 2005;Lam et al 2006;Huang et al 2007;Bertrand and Hobert 2009).…”

“…Several in vitro and in vivo analyses of TCF family members indicate a preference for the core DNA site CTTTGWW (Arce et al 2006;Hatzis et al 2008;MacDonald et al 2009). Although few bona fide POP-1 targets are known in C. elegans, it is clear that POP-1 also binds to sites with a T instead of a C nucleotide in the first position (e.g., TTTTGAT in ceh-13 and psa-3 [Streit et al 2002;Arata et al 2006] and TTTTGAA in ceh-22 [Lam et al 2006]). Based on the structure of LEF-1 bound to DNA, POP-1 differs from other TCF family members in amino acid sequence where contact is made at the first nucleotide of the core site (Love et al 1995).…”

The Caenorhabditis elegans SOMI-1 zinc finger protein and SWI/SNF promote regulation of development by the mir-84 microRNA

“…For example, the larval asymmetric division of the T cell, the most posterior of the seam cells, which differentiate under the control of let-7 at the adult stage, is regulated by SWI/SNF, together with Wnt signaling (Sawa et al 2000), the Hox protein NOB-1/Abd, and cofactors PSA-3/Meis and CEH-20/Pbx (Arata et al 2006), and the nuclear hormone receptor encoded by nhr-25 (Hajduskova et al 2009), itself a target of let-7 ). SOMI-1 may promote alterations in chromatin structure, mediated by a PBAF-like complex, that occur in response to expression of mir-84 and let-7 and oppose the activity of larval fate-promoting factors.…”