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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

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.

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    Title
    • Layer Specific and General Requirements for ERK/MAPK Signaling in the Developing Neocortex
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    Date Created
    2016-02-05
    Resource Type
  • Text
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    Identifier
    • Digital object identifier: 10.7554/eLife.11123
    • Identifier Type
      International standard serial number
      Identifier Value
      2050-084X

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    Xing, L., Larsen, R. S., Bjorklund, G. R., Li, X., Wu, Y., Philpot, B. D., . . . Newbern, J. M. (2016). Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex. ELife, 5. doi:10.7554/elife.11123

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