Disruption of wave-associated Rac GTPase-activating protein (Wrp) leads to abnormal adult neural progenitor migration associated with hydrocephalus

Il Hwan Kim, Benjamin R. Carlson, Clifford C. Heindel, Hyun Kim, Scott H. Soderling

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)39263-39274
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number46
DOIs
Publication statusPublished - 2012 Nov 9

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ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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