title: Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex.
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.
authors: University of North Carolina Neuroscience Center, The University of North Carolina School of Medicine, Chapel Hill, United States.
authors: Lei
authors: L
authors: Xing
authors: Allen Institute for Brain Science, Seattle, United States.
authors: Rylan S
authors: http://orcid.org/0000-0002-7136-1175
authors: RS
authors: Larsen
authors: School of Life Sciences, Arizona State University, Tempe, United States.
authors: George Reed
authors: GR
authors: Bjorklund
authors: University of North Carolina Neuroscience Center, The University of North Carolina School of Medicine, Chapel Hill, United States.
authors: Xiaoyan
authors: X
authors: Li
authors: University of North Carolina Neuroscience Center, The University of North Carolina School of Medicine, Chapel Hill, United States.
authors: Yaohong
authors: Y
authors: Wu
authors: University of North Carolina Neuroscience Center, The University of North Carolina School of Medicine, Chapel Hill, United States.|Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, United States.|Carolina Institute for Developmental Disabilities, The University of North Carolina School of Medicine, Chapel Hill, United States.
authors: Benjamin D
authors: BD
authors: Philpot
authors: University of North Carolina Neuroscience Center, The University of North Carolina School of Medicine, Chapel Hill, United States.|Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, United States.|Carolina Institute for Developmental Disabilities, The University of North Carolina School of Medicine, Chapel Hill, United States.
authors: William D
authors: WD
authors: Snider
authors: School of Life Sciences, Arizona State University, Tempe, United States.
authors: Jason M
authors: JM
authors: Newbern
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D020935:MAP Kinase Signaling System; D008822:Mice, Transgenic; D019579:Neocortex / Q000196:embryology*; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*
keywords: axon; corticospinal; developmental biology; excitability; excitatory neuron; kinase; mouse; neuroscience; stem cells