MBT domain proteins in development and disease

http://www.bosch.zoologie.uni-kiel.de/wp-content/uploads/2013/05/Transgenic-stem-cells-in-Hydra-reveal.pdf

Transgenic stem cells in Hydra reveal an early evolutionary origin for key elements controlling self-renewal and differentiation.

The Polycomb repression complex 2 (PRC2) methylates histone H3 lysine 27 at target genes to modify gene expression, and this mark is recognized by PRC1, which ubiquitylates histone H2A. In Caenorhabditis elegans , a complex of the MES-2, MES-3 and MES-6 proteins is functionally analogous to the PRC2 complex, but the functional analog of PRC1, and indeed whether C. elegans has such a complex, has been unclear. We describe here that MIG-32 and SPAT-3A are functional analogs of PRC1 in C. elegans , where they are required for neuronal migrations and during vulval development. mig-32 and spat-3 mutants are defective in H2A ubiquitylation, and have nervous system defects that partially overlap with those of mes mutants. However, unlike the mes mutants, mig-32 and spat-3 mutants are fertile, suggesting that PRC1 function is not absolutely required in the germline for essential functions of PRC2.

MIG-32 and SPAT-3A are PRC1 homologs that control neuronal migration in Caenorhabditis elegans.

Background: Reproduction in animals requires development of distinct neurons in each sex In C elegans, most ventral cord neurons (VCNs) are present in both sexes, with the exception of six hermaphrodite-specific neurons (VCs) and nine pairs of male-specific neurons (CAs and CPs) that arise from analogous precursor cells How are the activities of sexual regulators and mediators of neuronal survival, division, and fate coordinated to generate sex-specificity in VCNs? Results: To address this, we have developed a toolkit of VCN markers that allows us to examine sex-specific neurogenesis, asymmetric fates of daughters of a neuroblast division, and regional specification on the anteroposterior axis Here, we describe the roles of the Hox transcription factors LIN-39 and MAB-5 in promoting survival, differentiation, and regionalization of VCNs We also find that the TALE class homeodomain proteins CEH-20 and UNC-62 contribute to specification of neurotransmitter fate in males Furthermore, we identify that VCN sex is determined during the L1 larval stage Conclusions: These findings, combined with future analyses made possible by the suite of VCN markers described here, will elucidate how Hox-mediated cell fate decisions and sex determination intersect to influence development of neuronal sex differences Developmental Dynamics 243:159–171, 2014 © 2013 Wiley Periodicals, Inc

https://anatomypubs.onlinelibrary.wiley.com/doi/pdf/10.1002/dvdy.24043

Patterning of sexually dimorphic neurogenesis in the Caenorhabditis elegans ventral cord by Hox and TALE homeodomain transcription factors

In Caenorhabditis elegans, the domains of Hox gene expression are controlled by the novel global regulatory gene sop-2. We identified a region located 3′ of the Hox gene egl-5 that promotes ectopic expression of an egl-5 reporter gene in a sop-2 mutant. SOP-2 could directly block positive regulatory factors acting in this region, or it could block their expression. We identified three possible miRNA binding sites within the egl-5 3′ untranslated region (UTR). Cognate microRNAs are expressed in relevant tissues and can block egl-5 expression when expressed from a transgene. Mutation of the putative binding sites in the egl-5 3′UTR resulted in a modest degree of misexpression of a minimal egl-5 reporter gene, suggesting that microRNAs may contribute to the tight restriction of egl-5 expression to particular cell lineages. Developmental Dynamics 238:595–603, 2009. © 2009 Wiley-Liss, Inc.

Regulation of the Caenorhabditis elegans posterior Hox gene egl-5 by microRNA and the polycomb-like gene sop-2.

The molecular mechanisms underlying the formation of neurons with defined neurotransmitters are not well understood. In this study, we demonstrate that the PcG-like genes in Caenorhabditis elegans, sop-2 and sor-3, regulate the formation of dopaminergic and serotonergic neurons and several other neuronal properties. sor-3 encodes a novel protein containing an MBT repeat, a domain that contains histone-binding activity and is present in PcG proteins SCM and Sfmbt in other organisms. We further show that mutations in sor-3 lead to ectopic expression of Hox genes and cause homeotic transformations. Specification of certain neuronal identities by these PcG-like genes appears to involve regulation of non-Hox gene targets. Our studies revealed that the PcG-like genes are crucial for coordinately regulating the expression of discrete aspects of neuronal identities in C. elegans.

Polycomb-like genes are necessary for specification of dopaminergic and serotonergic neurons in Caenorhabditis elegans.

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Polycomb-like genes are necessary for specification of dopaminergic and serotonergic neurons in Caenorhabditis elegans.