Abstract：
:Dentate gyrus (DG) development requires specification of granule cell (GC) progenitors in the hippocampal neuroepithelium, as well as their proliferation and migration into the primordial DG. We identify the Plexin family members Plxna2 and Plxna4 as important regulators of DG development. Distribution of immature GCs is regulated by Sema5A signaling through PlxnA2 and requires a functional PlxnA2 GTPase-activating protein (GAP) domain and Rap1 small GTPases. In adult Plxna2-/- but not Plxna2-GAP-deficient mice, the dentate GC layer is severely malformed, neurogenesis is compromised, and mossy fibers form aberrant synaptic boutons within CA3. Behavioral studies with Plxna2-/- mice revealed deficits in associative learning, sociability, and sensorimotor gating-traits commonly observed in neuropsychiatric disorder. Remarkably, while morphological defects are minimal in Plxna2-GAP-deficient brains, defects in fear memory and sensorimotor gating persist. Since allelic variants of human PLXNA2 and RAP1 associate with schizophrenia, our studies identify a biochemical pathway important for brain development and mental health.
journal_name
Cell Repjournal_title
Cell reportsauthors
Zhao XF,Kohen R,Parent R,Duan Y,Fisher GL,Korn MJ,Ji L,Wan G,Jin J,Püschel AW,Dolan DF,Parent JM,Corfas G,Murphy GG,Giger RJdoi
10.1016/j.celrep.2017.12.044subject
Has Abstractpub_date
2018-01-09 00:00:00pages
456-470issue
2issn
2211-1247pii
S2211-1247(17)31868-5journal_volume
22pub_type
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