期刊
JOURNAL OF COMPARATIVE NEUROLOGY
卷 521, 期 3, 页码 677-696出版社
WILEY
DOI: 10.1002/cne.23199
关键词
brain development; axon guidance; cortical lamination; corticothalamic axons; chaperone; Hspa5; mouse; ENU mutant; protein misfolding; UPR; endoplasmic reticulum; heat shock protein
资金
- National Institutes of Health [K01MH069647, R01HD36404, R01MH081187]
- University of Virginia Fund for Excellence in Science and Technology
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. J. Comp. Neurol. 521:677696, 2013. (c) 2012 Wiley Priodcals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据