title: Expression of dystroglycan, fukutin and POMGnT1 during mouse cerebellar development.
abstract: Dystroglycan (DG) plays a central role in linking the extracellular matrix to cellular cytoskeletal elements, and is required for proper neuromuscular junction organization and neural cell migration in the CNS. DG interactions with laminin and several other extracellular ligands are mediated through carbohydrates located in a densely glycosylated mucin core domain on alpha-DG. A hallmark of a number of congenital muscular dystrophies is abnormal alpha-DG glycosylation and disordered neuronal migration in both the cerebral cortex and cerebellum. The underlying genetic defects in two such diseases have been localized to the POMGnT1 glycosyltransferase and the putative glycosyltransferase fukutin. We report here the spatial expression pattern of DG together with its putative modifying enzymes during the period of peak neuronal migration in the cerebellum. All three genes are broadly expressed in late embryonic and early postnatal cerebellar neurons, including premigratory granule neurons of the external granule cell layer. Expression of POMGnT1 and fukutin is maintained in neurons of the internal granule cell layer after migration is complete, whereas DG mRNA is largely downregulated. Purkinje cells expressed all three genes throughout development at varying levels, ranging from weak expression of DG to a unique pattern of intense fukutin expression in irregularly spaced cell bodies that do not appear to correlate with known parasagittal stripes. Significantly, immunocytochemical analysis reveals that alpha- and beta-DG proteins are also present on the Bergmann glial scaffolds used by granule cells during early postnatal radial migration, and double-label in situ hybridization confirms that these cells also express POMGnT1 and fukutin. These results suggest that abnormal glycosylation of alpha-DG on glial scaffolds and neurons and their processes could affect interactions with alpha-DG ligands expressed by migrating granule cells, and be a potential mechanism through which neuronal migration is compromised in CMD disease.
authors.affiliation: Shriver Center for Mental Retardation, 200 Trapelo Road, Waltham, MA 02452, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Henion
authors.forename: Qiang
authors.initials: Q
authors.lastname: Qu
authors.forename: Frances I
authors.initials: FI
authors.lastname: Smith
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D049030:Dystroglycans; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006031:Glycosylation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014166:Transferases
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D011506:Proteins; D012333:RNA, Messenger; D049030:Dystroglycans; C491879:Fcmd protein, mouse; D014166:Transferases; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase