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DRR1, Fam107A, Tu3A, Fam107B, HITS, stress, corticogenesis, glucocorticoid receptor
Abstract:
Understanding the molecular mechanisms that promote stress resilience
might open up new therapeutic avenues to prevent stress-related
disorders. We recently characterized a stress and
glucocorticoid-regulated gene, down-regulated in renal cell carcinoma -
DRR1 (Fam107A). DRR1 is expressed in the mouse brain; it is up-regulated
by stress and glucocorticoids and modulates neuronal actin dynamics. In
the adult mouse, DRR1 was shown to facilitate specific behaviors which
might be protective against some of the deleterious consequences of
stress exposure: in the hippocampal CA3 region, DRR1 improved cognitive
performance whereas in the septum, it specifically increased social
behavior. Therefore DRR1 was suggested as a candidate protein promoting
stress-resilience. Fam107B (family with sequence similarity 107, member
B) is the unique paralog of DRR1, and both share high sequence
similarities, predicted glucocorticoid response elements, heat-shock
induction and tumor suppressor properties. So far, the role of Fam107B
in the central nervous system was not studied. The aim of the present
investigation, therefore, was to analyze whether Fam107B and DRR1
display comparable mRNA expression patterns in the brain and whether
both are modulated by stress and glucocorticoids. Spatio-temporal
mapping of Fam107B mRNA expression in the embryonic and adult mouse
brain, by means of in situ hybridization, showed that Fam107B was
expressed during embryogenesis and in the adulthood, with particularly
high and specific expression in the forming telencephalon suggestive of
an involvement in corticogenesis. In the adult mouse, expression was
restricted to neurogenic niches, like the dentate gyrus. In contrast to
DRR1, Fam107B mRNA expression failed to be modulated by glucocorticoids
and social stress in the adult mouse. In summary, Fam107B and DRR1 show
different spatio-temporal expression patterns in the central nervous
system, suggesting at least partially different functional roles in the
brain, and where the glucocorticoid receptor (GR)-induced regulation
appears to be a unique property of DRR1. (C) 2015 IBRO. Published by
Elsevier Ltd. All rights reserved.
