1. Mutation of the BiP/GRP78 gene causes axon outgrowth and fasciculation defects in the thalamocortical connections of the mammalian forebrain.
- Author
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Favero CB, Henshaw RN, Grimsley-Myers CM, Shrestha A, Beier DR, and Dwyer ND
- Subjects
- Animals, Cells, Cultured, Cerebral Cortex cytology, Cerebral Cortex physiology, Endoplasmic Reticulum Chaperone BiP, Female, Fibroblasts cytology, Genetic Testing, Gestational Age, Male, Mammals, Mice, Mice, Inbred C57BL, Mice, Neurologic Mutants, Neural Pathways abnormalities, Neural Pathways cytology, Neural Pathways physiology, Pregnancy, Prosencephalon abnormalities, Prosencephalon cytology, Prosencephalon physiology, Thalamus cytology, Thalamus physiology, Axons physiology, Cerebral Cortex abnormalities, Heat-Shock Proteins genetics, Thalamus abnormalities
- Abstract
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., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2013
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