title: Dystroglycan regulates structure, proliferation and differentiation of neuroepithelial cells in the developing vertebrate CNS.
abstract: In the developing CNS alpha- and beta-dystroglycan are highly concentrated in the endfeet of radial neuroepithelial cells at the contact site to the basal lamina. We show that injection of anti-dystroglycan Fab fragments, knockdown of dystroglycan using RNAi, and overexpression of a dominant-negative dystroglycan protein by microelectroporation in neuroepithelial cells of the chick retina and optic tectum in vivo leads to the loss of their radial morphology, to hyperproliferation, to an increased number of postmitotic neurons, and to an altered distribution of several basally concentrated proteins. Moreover, these treatments also altered the oriented growth of axons from retinal ganglion cells and from tectal projection neurons. In contrast, expression of non-cleavable dystroglycan protein in neuroepithelial cells reduced their proliferation and their differentiation to postmitotic neurons. These results demonstrate that dystroglycan plays a key role in maintaining neuroepithelial cell morphology, and that interfering with dystroglycan function influences proliferation and differentiation of neuroepithelial cells. These data also suggest that an impaired dystroglycan function in neuroepithelial cells might be responsible for some of the severe brain abnormalities observed in certain forms of congenital muscular dystrophy.
authors.affiliation: Department of Physiological Chemistry, University of Mainz, Duesbergweg 6, D-55099 Mainz, Germany.
authors.forename: Jörn E
authors.initials: JE
authors.lastname: Schröder
authors.forename: Marion R
authors.initials: MR
authors.lastname: Tegeler
authors.forename: Uli
authors.initials: U
authors.lastname: Grosshans
authors.forename: Elmar
authors.initials: E
authors.lastname: Porten
authors.forename: Martina
authors.initials: M
authors.lastname: Blank
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.forename: Chris
authors.initials: C
authors.lastname: Esapa
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Blake
authors.forename: Stephan
authors.initials: S
authors.lastname: Kröger
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D002490:Central Nervous System / Q000254:growth & development*; D002645:Chickens; D049030:Dystroglycans / Q000502:physiology*; D009136:Muscular Dystrophies / Q000503:physiopathology; D046569:Neuroepithelial Cells / Q000166:cytology*; D012160:Retina / Q000166:cytology; D013477:Superior Colliculi / Q000166:cytology; D014714:Vertebrates
chemical_list: D049030:Dystroglycans