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Mutation of the BiP/GRP78 gene causes axon outgrowth and fasciculation defects in the thalamocortical connections of the mammalian forebrain
Author(s) -
Favero Carlita B.,
Henshaw Rasha N.,
GrimsleyMyers Cynthia M.,
Shrestha Ayushma,
Beier David R.,
Dwyer Noelle D.
Publication year - 2012
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.23199
Subject(s) - axon , forebrain , biology , neuroscience , axon guidance , mutant , endoplasmic reticulum , fasciculation , microbiology and biotechnology , cerebral cortex , thalamus , neurite , genetics , gene , central nervous system , in vitro
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. 521:677–696, 2013. © 2012 Wiley Priodcals, Inc.