PT  - JOURNAL ARTICLE
AU  - Jakob S. Satz
AU  - Adam P. Ostendorf
AU  - Shangwei Hou
AU  - Amy Turner
AU  - Hajime Kusano
AU  - Jane C. Lee
AU  - Rolf Turk
AU  - Huy Nguyen
AU  - Susan E. Ross-Barta
AU  - Steve Westra
AU  - Toshinori Hoshi
AU  - Steven A. Moore
AU  - Kevin P. Campbell
TI  - Distinct Functions of Glial and Neuronal Dystroglycan in the Developing and Adult Mouse Brain
AID  - 10.1523/JNEUROSCI.3247-10.2010
DP  - 2010 Oct 27
TA  - The Journal of Neuroscience
PG  - 14560--14572
VI  - 30
IP  - 43
4099  - http://www.jneurosci.org/content/30/43/14560.short
4100  - http://www.jneurosci.org/content/30/43/14560.full
SO  - J. Neurosci.2010 Oct 27; 30
AB  - Cobblestone (type II) lissencephaly and mental retardation are characteristic features of a subset of congenital muscular dystrophies that include Walker–Warburg syndrome, muscle-eye-brain disease, and Fukuyama-type congenital muscular dystrophy. Although the majority of clinical cases are genetically undefined, several causative genes have been identified that encode known or putative glycosyltransferases in the biosynthetic pathway of dystroglycan. Here we test the effects of brain-specific deletion of dystroglycan, and show distinct functions for neuronal and glial dystroglycan. Deletion of dystroglycan in the whole brain produced glial/neuronal heterotopia resembling the cerebral cortex malformation in cobblestone lissencephaly. In wild-type mice, dystroglycan stabilizes the basement membrane of the glia limitans, thereby supporting the cortical infrastructure necessary for neuronal migration. This function depends on extracellular dystroglycan interactions, since the cerebral cortex developed normally in transgenic mice that lack the dystroglycan intracellular domain. Also, forebrain histogenesis was preserved in mice with neuron-specific deletion of dystroglycan, but hippocampal long-term potentiation was blunted, as is also the case in the Largemyd mouse, in which dystroglycan glycosylation is disrupted. Our findings provide genetic evidence that neuronal dystroglycan plays a role in synaptic plasticity and that glial dystroglycan is involved in forebrain development. Differences in dystroglycan glycosylation in distinct cell types of the CNS may contribute to the diversity of dystroglycan function in the CNS, as well as to the broad clinical spectrum of type II lissencephalies.