Direct Regulation of Adult Brain Function by the Male-Specific Factor SRY

1. Curr Biol. 2006 Feb 21;16(4):415-20. doi: 10.1016/j.cub.2006.01.017.

Direct regulation of adult brain function by the male-specific factor SRY.

Dewing P(1), Chiang CW, Sinchak K, Sim H, Fernagut PO, Kelly S, Chesselet MF,
Micevych PE, Albrecht KH, Harley VR, Vilain E.

Author information:
(1)Department of Human Genetics, University of California, Los Angeles, Los
Angles, California 90095, USA.

The central dogma of mammalian brain sexual differentiation has contended that
sex steroids of gonadal origin organize the neural circuits of the developing
brain. Recent evidence has begun to challenge this idea and has suggested that,
independent of the masculinizing effects of gonadal secretions, XY and XX brain
cells have different patterns of gene expression that influence their
differentiation and function. We have previously shown that specific differences
in gene expression exist between male and female developing brains and that
these differences precede the influences of gonadal hormones. Here we
demonstrate that the Y chromosome-linked, male-determining gene Sry is
specifically expressed in the substantia nigra of the adult male rodent in
tyrosine hydroxylase-expressing neurons. Furthermore, using antisense
oligodeoxynucleotides, we show that Sry downregulation in the substantia nigra
causes a statistically significant decrease in tyrosine hydroxylase expression
with no overall effect on neuronal numbers and that this decrease leads to motor
deficits in male rats. Our studies suggest that Sry directly affects the
biochemical properties of the dopaminergic neurons of the nigrostriatal system
and the specific motor behaviors they control. These results demonstrate a
direct male-specific effect on the brain by a gene encoded only in the male
genome, without any mediation by gonadal hormones.

DOI: 10.1016/j.cub.2006.01.017
PMID: 16488877 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus