Sex differences in X-linked gene expression in embryonic hypothalamic neurons

CABRERA ZAPATA, L.E.; CISTERNAS, C.D.; CAMBIASSO, M.J.

Congreso; XXXII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2017

Sociedad Argentina de Investigación en Neurociencias (SAN)

Although sex hormones are usually considered the main architects ofsexual dimorphisms, recent studies have demonstrated that sex chromosomes canalso induce sex differences in somatic gene expression in the absence ofhormonal differences. Ngn3 is aNotch regulated gene that, in developing neurons, is involved in neuriteextension and remodeling. Previous results showed that hypothalamic neuronscarrying the XX sex chromosomespresent a higher expression of Ngn3 and a faster rate of development than XYneurons, irrespectively of gonadal hormones. Using the Four Core Genotypes(FCG) mouse model, here we analyzed the expression of X-linked genes involved in neuronal growth and differentiationwhich are probable candidates to regulate Ngn3 expression. By qPCR, we have evaluatedthe expression of Ddx3x, Eif2s3x, Kdm6a, Syp, Mecp2 and Usp9x in primary hypothalamic cultures from E15 FCG mice. Ddx3x, Eif2s3x and Kdm6a showedhigher expression levels in XX neuronsthan in XY neurons, regardless of theembryo sex. Importantly, Kdm6a is anepigenetic regulator codifying for a histone demethylase, whereas Ddx3x and Eif2s3x codify translation regulators. Thereby, it is possible tohypothesize that some of these genes might be regulating Ngn3 expression andneuronal development. Further experiments blocking these X-linked genes are required to determine the effect of this specificdown regulation over Ngn3 and neuronal development. Financial support: CONICET, ANPCyT and SECyT-UNC.