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

Abstract

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. V C 2013 Wiley Periodicals, Inc.Key words: C. elegans; Hox genes; sexual dimorphism; neurogenesis; TALE homeodomain proteins; male-specific neurons; ventral cord neurons Key Findings:C. elegans male and hermaphrodite ventral nerve cords are sexually distinct with sex determination occurring during the first larval stage. Hox genes lin-39 and mab-5 influence multiple events in neurogenesis and function in partially overlapping regions in the ventral nerve cord. TALE homeodomain genes ceh-20 and unc-62 are required with lin-39 to specify serotonergic fate in male ventral cord neurons. unc-3 prevents inappropriate serotonergic specification in both males and hermaphrodites.

Cellular and molecular insights into Hox protein action

“…The C. elegans LIN-39 Hox protein suppresses inappropriate apoptosis in male-specific serotoninergic neuron precursors (Kalis et al, 2014), and MAB-5, another C. elegans Hox protein, directly controls apoptosis in proneural ventral blast cells (Liu et al, 2006). Hoxd gene deletions cause an up to 6-fold increase in apoptosis during kidney development in mice (Di-Poї et al, 2007).…”

Sexual modulation of neural circuits and behavior in Caenorhabditis elegans

“…This genetic logic is reversed in the case of the CEMs, where tra-1 represses ceh-30 , a pro-survival homeodomain transcription factor, to cause cell death in hermaphrodites and survival in males [15,16]. In the case of other sex-specific neurons, tra-1 acts in more complex means to regulate the proliferation of neural precursors and specification of cell fate [17,18]. In these cases, the specific mechanisms by which tra-1 brings about sex differences in neuroanatomy remain unclear.…”

Visualizing the organization and differentiation of the male-specific nervous system ofC. elegans

“…With some notable exceptions, including the systematic mapping of neurotransmitter identities (Gendrel et al, 2016;Pereira et al, 2015;Serrano-Saiz et al, 2017), marker analysis in the ray sensory neurons (Lints et al, 2004) and ventral nerve cord (Kalis et al, 2014), few molecular markers have been developed that label male-specific neurons. Single-cell transcriptome approaches have so far exclusively focused on the hermaphrodite (Cao et al, 2017;Packer et al, 2019;Taylor et al, 2020).…”