Sex-specific regulation of neuronal functions in Caenorhabditis elegans: the sex-determining protein TRA-1 represses goa-1/Gα(i/o)

Abstract

Females and males differ substantially in various neuronal functions in divergent, sexually dimorphic animal species, including humans. Despite its developmental, physiological and medical significance, understanding the molecular mechanisms by which sex-specific differences in the anatomy and operation of the nervous system are established remains a fundamental problem in biology. Here, we show that in Caenorhabditis elegans (nematodes), the global sex-determining factor TRA-1 regulates food leaving (mate searching), male mating and adaptation to odorants in a sex-specific manner by repressing the expression of goa-1 gene, which encodes the Gα (i/o) subunit of heterotrimeric G (guanine-nucleotide binding) proteins triggering physiological responses elicited by diverse neurotransmitters and sensory stimuli. Mutations in tra-1 and goa-1 decouple behavioural patterns from the number of X chromosomes. TRA-1 binds to a conserved binding site located in the goa-1 coding region, and downregulates goa-1 expression in hermaphrodites, particularly during embryogenesis when neuronal development largely occurs. These data suggest that the sex-determination machinery is an important modulator of heterotrimeric G protein-mediated signalling and thereby various neuronal functions in this organism and perhaps in other animal phyla.

Sulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan

“…Three fem genes directly regulate the expression of tra-1 . Loss of function of fem-3 results in the hyperactivity of TRA-1 expression ( Szabó et al, 2009 ; Kutnyánszky et al, 2020 ) and promotes the development of hermaphrodites ( Starostina et al, 2007 ). TRA-1 is orthologous to the human GLI protein, a mediator of Sonic hedgehog signaling, which is involved in embryonic limb development ( Briscoe and Thérond, 2013 ), but also in tumorigenesis ( Coquenlorge et al, 2019 ), and was most recently identified as a suppressor of endometrial stem cell aging ( Cho et al, 2019 ).…”