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Media type:
E-Article
Title:
Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex
Contributor:
Xing, Lei;
Larsen, Rylan S;
Bjorklund, George Reed;
Li, Xiaoyan;
Wu, Yaohong;
Philpot, Benjamin D;
Snider, William D;
Newbern, Jason M
imprint:
eLife Sciences Publications, Ltd, 2016
Published in:eLife
Language:
English
DOI:
10.7554/elife.11123
ISSN:
2050-084X
Origination:
Footnote:
Description:
<jats:p>Aberrant signaling through the Raf/MEK/ERK (ERK/MAPK) pathway causes pathology in a family of neurodevelopmental disorders known as 'RASopathies' and is implicated in autism pathogenesis. Here, we have determined the functions of ERK/MAPK signaling in developing neocortical excitatory neurons. Our data reveal a critical requirement for ERK/MAPK signaling in the morphological development and survival of large Ctip2+ neurons in layer 5. Loss of Map2k1/2 (Mek1/2) led to deficits in corticospinal tract formation and subsequent corticospinal neuron apoptosis. ERK/MAPK hyperactivation also led to reduced corticospinal axon elongation, but was associated with enhanced arborization. ERK/MAPK signaling was dispensable for axonal outgrowth of layer 2/3 callosal neurons. However, Map2k1/2 deletion led to reduced expression of Arc and enhanced intrinsic excitability in both layers 2/3 and 5, in addition to imbalanced synaptic excitation and inhibition. These data demonstrate selective requirements for ERK/MAPK signaling in layer 5 circuit development and general effects on cortical pyramidal neuron excitability.</jats:p>