Role of X-linked genes on sex differences in neurogenin 3 expression in developing hypothalamic neurons

CISTERNAS, C.D.; AREVALO, M.A.; GARCIA-SEGURA, L.M.; CAMBIASSO, M.J.

CABA

Congreso; 2do. Congreso de la Federación de Sociedades de Neurociencias de Latinoamérica y el Caribe (FALAN); 2016

Sexchromosome complement regulates the generation of sex differences in mousehypothalamic neuronal development. The higher expression of neurogenin 3 (Ngn3)in XX hypothalamic neurons mediates sex differences in the rate of neuronaldifferentiation. Since Ngn3 is an autosomal gene these imply that sex chromosomescan induce sex differences in somatic gene expression during development. Herewe tested the hypothesis that X genes that escape X-inactivation are involvedin regulation of sex differences inautosomal expression of Ngn3 in hypothalamic neurons. To deal this aimwe evaluated by qPCR the expression of Ddx3x, Eif2s3x, Kdm5c, Kdm6a, Mid1 andUsp9x in primary neuronal culture from E14 male and female mice. Female neuronsshowed enhanced expression of Usp9x (p<0.05) which encodes for a deubiquitinatingenzyme (DUB) highly expressed in developing brain. We next evaluated the effectof DUB inhibitor WP1130 on Ngn3 expression. Our preliminary results showed thatWP1130 increases Ngn3 expression only in male neurons (p<0.05) abolishingsex differences. These findings suggest that the X-linked gene Usp9x regulatesthe expression of the autosomal gene Ngn3 which is involved in sex differencesin hypothalamic neuronal development. Since WP1130 is a partly selective DUBinhibitor further experiments are required to determine the effect of specific downregulation of Usp9x expression on the observed sex differences in growth anddifferentiation of hypothalamic neurons. Financial support: CONICET, ANPCyT and SECyT-UNC,Argentina.