Jagged1 ablation results in cerebellar granule cell migration defects and depletion of Bergmann glia.
Jagged1 is a ligand for members of the Notch family of receptors. Mutations in the human JAG1 gene are the major cause of Alagille syndrome, an autosomal dominant disorder affecting the liver, heart, eye, skeleton, kidneys, and craniofacial structures. Although expressed throughout mammalian embryonic development and in the adult, the function of Jagged1 in the central nervous system is not clear. Jagged1 is broadly expressed in the cerebellum suggesting an important role in Notch signaling. In order to address the function of Jagged1 in the mouse central nervous system, we have inactivated the Jag1 gene in the cerebellar primordium at mid-embryogenesis. Loss of Jagged1 results in aberrant granule cell migration and ectopic differentiation in the external germinal layer and molecular layer of the early postnatal cerebellum. We show that Bergmann glia in the cerebellum lose contact to the pial surface and have stunted processes. In vitro analysis revealed a depletion of Bergmann glia in the Jagged1 mutant mice. Our findings suggest that Jagged1 plays a role in cell fate specification and survival in the cerebellum.
Weller
Mathias
M
Department of Molecular Embryology, Max Planck Institute of Immunobiology, Freiburg, Germany.
Krautler
Nike
N
Mantei
Ned
N
Suter
Ueli
U
Taylor
Verdon
V
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D048430:Cell Shape / Q000235:genetics; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D000072099:Serrate-Jagged Proteins
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D000072099:Serrate-Jagged Proteins