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J Comp Neurol ; 521(3): 677-96, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22821687

RESUMO

Proper development of axonal connections is essential for brain function. A forward genetic screen for mice with defects in thalamocortical development previously isolated a mutant called baffled. Here we describe the axonal defects of baffled in further detail and identify a point mutation in the Hspa5 gene, encoding the endoplasmic reticulum chaperone BiP/GRP78. This hypomorphic mutation of BiP disrupts proper development of the thalamocortical axon projection and other forebrain axon tracts, as well as cortical lamination. In baffled mutant brains, a reduced number of thalamic axons innervate the cortex by the time of birth. Thalamocortical and corticothalamic axons are delayed, overfasciculated, and disorganized along their pathway through the ventral telencephalon. Furthermore, dissociated mutant neurons show reduced axon extension in vitro. Together, these findings demonstrate a sensitive requirement for the endoplasmic reticulum chaperone BiP/GRP78 during axon outgrowth and pathfinding in the developing mammalian brain.


Assuntos
Axônios/fisiologia , Córtex Cerebral/anormalidades , Proteínas de Choque Térmico/genética , Tálamo/anormalidades , Animais , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/fisiologia , Chaperona BiP do Retículo Endoplasmático , Feminino , Fibroblastos/citologia , Testes Genéticos , Idade Gestacional , Masculino , Mamíferos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes Neurológicos , Vias Neurais/anormalidades , Vias Neurais/citologia , Vias Neurais/fisiologia , Gravidez , Prosencéfalo/anormalidades , Prosencéfalo/citologia , Prosencéfalo/fisiologia , Tálamo/citologia , Tálamo/fisiologia
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