A direct glia-to-neuron natural transdifferentiation ensures nimble sensory-motor coordination of male mating behaviour

Abstract

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism to generate male-specific neurons in Caenorhabditis elegans, through the direct transdifferentiation of sex-shared glial cells. This glia-to-neuron cell fate switch occurs during male sexual maturation under the cell-autonomous control of the sex-determination pathway. We show that the neurons generated are cholinergic, peptidergic and ciliated putative proprioceptors which integrate into male-specific circuits for copulation. These neurons ensure coordinated backward movement along the mate's body during mating. One step of the mating sequence regulated by these neurons is an alternative readjustment movement performed when intromission becomes difficult to achieve. Our findings reveal programmed transdifferentiation as a developmental mechanism underlying flexibility in innate behaviour.

Glutamate in Male and Female Sexual Behavior: Receptors, Transporters, and Steroid Independence

“…In terms of glia affecting sexual behavior, Grosjean et al (2008) demonstrated in male Drosophila melanogaster a glial aminoacid transporter regulated courtship and copulatory behavior toward other males. A more recent study showed that in male Caenorhabditis elegans, transdifferentiation occurs in glial cells that convert to neurons important for copulation (Molina-García et al, 2018). There abide a paucity of knowledge on how glia regulates sexual behavior, and given their critical role in regulating glutamate, future experiments can help elucidate the specific role of glia on glutamatergic signaling in sexual behavior.…”

Automated analysis of sleep in adultC. eleganswith closed-loop assessment of state-dependent neural activity

“…The nematode C. elegans provides distinct advantages for direct observation of neurological function in freely-behaving animals. They are small (<1 mm), exhibit short generational times, and have a compact and fully mapped connectome of 302 neurons in hermaphrodites and 387 in males 21 . Noninvasive optical measurements of neural activity can be made in living, behaving animals via genetically-encoded fluorescent calcium indicators such as GCaMP 22 , and genetic tools are available for rapid generation of mutants and transgenic strains for mechanistic studies [23][24][25] .…”

A Pipeline for Volume Electron Microscopy of the Caenorhabditis elegans Nervous System

“…Third, sexual dimorphism is prominent in the C. elegans nervous system. Compared to adult hermaphrodites, adult males have an additional 85 neurons, accounting for ∼20% of the nervous system ( Sulston and Horvitz, 1977 ; Sulston et al, 1980 ; Sammut et al, 2015 ; Molina-Garcia et al, 2018 ). Though progress has been made on the wiring of parts of the male nervous system ( Hall and Russell, 1991 ; Jarrell et al, 2012 ), a complete and comprehensive side-by-side comparison of high-quality male and hermaphrodite connectomes awaits.…”