The nuclear receptor NHR-25 cooperates with the Wnt/β-catenin asymmetry pathway to control differentiation of the T seam cell inC. elegans

Abstract

Asymmetric cell divisions produce daughter cells with distinct developmental fates, therefore representing a key mechanism of tissue and organ differentiation during animal development (Betschinger and Knoblich, 2004;Roegiers and Jan, 2004; Gönczy, 2008). Cell commitment to a particular fate depends on establishment of a polarity axis, orientation of mitotic spindle along this axis and asymmetric segregation of cell-fate determinants. These processes are ensured by precise spatial and temporal cellular signaling. The Caenorhabditis elegans model has been instrumental for understanding the genetics and molecular biology of cell-fate determination, because worm development relies heavily on asymmetric cell divisions (Sulston et al., 1983;Sulston and Horvitz, 1977). Signal-transduction pathways including Notch, Wnt/β-catenin and G-protein signaling regulate asymmetric cell divisions during early embryogenesis, differentiation of the epidermal stem cells, the somatic gonad and the germline, and morphogenesis of the vulva (Gönczy, 2008;Kimble and Crittenden, 2007;Mizumoto and Sawa, 2007b).The epidermal stem cells in C. elegans, known as the seam cells, provide an excellent system in which to study asymmetric cell divisions during postembryonic development. The seam cells divide asymmetrically to produce a copy of themselves and a differentiated cell, either a hypodermal cell or a neuron, depending on the seamcell position (Sulston and Horvitz, 1977). The posterior seam cells V5, V6 and T are extensively studied. Already at its first division the T seam cell generates anterior (T.a) and posterior (T.p) daughters with distinct fates. The T.a daughter assumes a hypodermal fate, whereas T.p gives rise to neural cells. Divisions of the T-seam-cell lineage differ between hermaphrodites and males. At the L2 stage in males, the T.ap (posterior daughter of T.a) cell together with posterior daughters of the V5 and V6 seam cells begins to generate male-specific sensory rays that are essential for mating.Differentiation of the T seam cell relies on proper establishment of its polarity, which is controlled by the Wnt/β-catenin asymmetry pathway (Herman, 2002;Herman and Wu, 2004;Mizumoto and Sawa, 2007b). A LIN-44/Wnt (C. elegans/ mammalian homolog) signal from the epidermal tail tip cells activates its receptor LIN-17/Frizzled, localized to the posterior membrane of the T seam cell (Wu and Herman, 2007). The signal ensures asymmetric distribution of APR-1/APC, PRY-1/Axin, LIT-1/NLK and WRM-1/β-catenin in the T seam cell (Mizumoto and Sawa, 2007a;Mizumoto and Sawa, 2007b), leading to uneven inheritance of these cell-fate determinants by the T.a and T.p daughters. In the T.p cell nucleus, abundant WRM-1/β-catenin and LIT-1/NLK facilitate export of the POP-1/TCF transcription factor from the nucleus. The remaining POP-1/TCF associates with its cofactor SYS-1/β-catenin (Kidd et al., 2005), which is enriched in the T.p nucleus, and activates neural-fate-promoting genes, exemplified by tlp-1. By contrast, the anterior T.a daughter is ...

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.…”

Collaborative Regulation of Development but Independent Control of Metabolism by Two Epidermis-specific Transcription Factors in Caenorhabditis elegans

“…The protein was also involved in controlling fat uptake and storage by regulating acyl-CoA synthase-3 activities (13). In addition, NHR-25 cooperates with the Wnt signaling pathway to control fate differentiation of T seam cells and somatic gonad (14). Despite dramatic expansion of the NHR family, genome-wide binding targets have not been determined for any member of the family in C. elegans.…”

The nuclear receptor gene nhr-25 plays multiple roles in the Caenorhabditis elegans heterochronic gene network to control the larva-to-adult transition

“…Previous studies have demonstrated that loss of nhr-25 function causes various phenotypes throughout development, such as defects on embryogenesis, differentiation of larval epidermis, molting, distal tip cell/anchor cell formation, and cell-cell fusion in vulval morphogenesis (Asahina et al, 2000; Asahina et al, 2006; Chen et al, 2004; Gissendanner and Sluder, 2000; Hajduskova et al, 2009; Silhankova et al, 2005). These observed phenotypes are the result of earlier or very severe knock-down and may have masked later or alternative functions.…”

“…nhr-25 belongs to the evolutionarily conserved nuclear receptor NR5A subfamily, including insect fushi tarazu-factor 1 (FTZ-F1) , mammalian steroidogenic factor 1 ( SF-1 ) and liver receptor homolog 1 ( LRH-1 ) (Asahina et al, 2000; Gissendanner and Sluder, 2000). Previous studies have shown that nhr-25 is necessary for a variety of developmental events, such as embryogenesis, hypodermal differentiation, exoskeleton production, vulval formation, and gonadal morphogenesis (Asahina et al, 2000; Asahina et al, 2006; Chen et al, 2004; Gissendanner and Sluder, 2000; Hajduskova et al, 2009; Silhankova et al, 2005). nhr-25 is also a downstream target of let-7 and other heterochronic genes involved in the cessation of molting (Hayes et al, 2006).…”