Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex

Lei Xing, Rylan S. Larsen, George Reed Bjorklund, Xiaoyan Li, Yaohong Wu, Benjamin D. Philpot, William D. Snider, Jason Newbern

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere11123
JournaleLife
Volume5
Issue numberFEBRUARY2016
DOIs
StatePublished - Feb 5 2016

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Xing, L., Larsen, R. S., Bjorklund, G. R., Li, X., Wu, Y., Philpot, B. D., Snider, W. D., & Newbern, J. (2016). Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex. eLife, 5(FEBRUARY2016), [e11123]. https://doi.org/10.7554/eLife.11123