title: A cell junction pathology of neural stem cells leads to abnormal neurogenesis and hydrocephalus.
abstract: Most cells of the developing mammalian brain derive from the ventricular (VZ) and the subventricular (SVZ) zones. The VZ is formed by the multipotent radial glia/neural stem cells (NSCs) while the SVZ harbors the rapidly proliferative neural precursor cells (NPCs). Evidence from human and animal models indicates that the common history of hydrocephalus and brain maldevelopment starts early in embryonic life with disruption of the VZ and SVZ. We propose that a "cell junction pathology" involving adherent and gap junctions is a final common outcome of a wide range of gene mutations resulting in proteins abnormally expressed by the VZ cells undergoing disruption. Disruption of the VZ during fetal development implies the loss of NSCs whereas VZ disruption during the perinatal period implies the loss of ependyma. The process of disruption occurs in specific regions of the ventricular system and at specific stages of brain development. This explains why only certain brain structures have an abnormal development, which in turn results in a specific neurological impairment of the newborn. Disruption of the VZ of the Sylvian aqueduct (SA) leads to aqueductal stenosis and hydrocephalus, while disruption of the VZ of telencephalon impairs neurogenesis. We are currently investigating whether grafting of NSCs/neurospheres from normal rats into the CSF of hydrocephalic mutants helps to diminish/repair the outcomes of VZ disruption.
authors.affiliation: Instituto de Anatomía, Histología y Patología, Universidad Austral de Chile, Valdivia, Chile. erodrigu@uach.cl
authors.forename: Esteban M
authors.initials: EM
authors.lastname: Rodríguez
authors.forename: María M
authors.initials: MM
authors.lastname: Guerra
authors.forename: Karin
authors.initials: K
authors.lastname: Vío
authors.forename: César
authors.initials: C
authors.lastname: González
authors.forename: Alexander
authors.initials: A
authors.lastname: Ortloff
authors.forename: Luis F
authors.initials: LF
authors.lastname: Bátiz
authors.forename: Sara
authors.initials: S
authors.lastname: Rodríguez
authors.forename: María C
authors.initials: MC
authors.lastname: Jara
authors.forename: Rosa I
authors.initials: RI
authors.lastname: Muñoz
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ortega
authors.forename: Jaime
authors.initials: J
authors.lastname: Jaque
authors.forename: Francisco
authors.initials: F
authors.lastname: Guerra
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Sival
authors.forename: Wilfred F A
authors.initials: WF
authors.lastname: den Dunnen
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Jiménez
authors.forename: María D
authors.initials: MD
authors.lastname: Domínguez-Pinos
authors.forename: José M
authors.initials: JM
authors.lastname: Pérez-Fígares
authors.forename: James P
authors.initials: JP
authors.lastname: McAllister
authors.forename: Conrad
authors.initials: C
authors.lastname: Johanson
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002535:Cerebral Aqueduct / Q000473:pathology; D002552:Cerebral Ventricles / Q000196:embryology / Q000473:pathology; D006801:Humans; D006849:Hydrocephalus / Q000473:pathology / Q000628:therapy*; D007365:Intercellular Junctions / Q000473:pathology*; D058953:Neural Stem Cells / Q000473:pathology* / Q000637:transplantation; D055495:Neurogenesis; D051381:Rats; D033581:Stem Cell Transplantation / Q000379:methods*