title: Disruption of wave-associated Rac GTPase-activating protein (Wrp) leads to abnormal adult neural progenitor migration associated with hydrocephalus.
abstract: Hydrocephalus is the most common developmental disability and leading cause of brain surgery for children. Current treatments are limited to surgical intervention, as the factors that contribute to the initiation of hydrocephalus are poorly understood. Here, we describe the development of obstructive hydrocephalus in mice that are null for Wrp (Srgap3). Wrp is highly expressed in the ventricular stem cell niche, and it is a gene required for cytoskeletal organization and is associated with syndromic and psychiatric disorders in humans. During the postnatal period of progenitor cell expansion and ventricular wall remodeling, loss of Wrp results in the abnormal migration of lineage-tagged cells from the ventricular region into the corpus callosum. Within this region, mutant progenitors appear to give rise to abnormal astroglial cells and induce periventricular lesions and hemorrhage that leads to cerebral aqueductal occlusion. These results indicate that periventricular abnormalities arising from abnormal migration from the ventricular niche can be an initiating cause of noncommunicating hydrocephalus.
authors.affiliation: Department of Cell Biology, Duke University Medical School, Durham, North Carolina 27710, USA.
authors.forename: Il Hwan
authors.initials: IH
authors.lastname: Kim
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Carlson
authors.forename: Clifford C
authors.initials: CC
authors.lastname: Heindel
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.forename: Scott H
authors.initials: SH
authors.lastname: Soderling
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002465:Cell Movement; D002552:Cerebral Ventricles / Q000166:cytology*; D005456:Fluorescent Dyes / Q000494:pharmacology; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D006849:Hydrocephalus / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: D005456:Fluorescent Dyes; D020690:GTPase-Activating Proteins; C516731:Srgap3 protein, mouse