Ephrin-A2 regulates excitatory neuron differentiation and interneuron migration in the developing neocortex

Jihane Homman-Ludiye, William C. Kwan, Mitchell J. De Souza, Jennifer Rodger, James A. Bourne

    Research output: Contribution to journalArticlepeer-review

    9 Citations (Scopus)

    Abstract

    The development of the neocortex requires co-ordination between proliferation and differentiation, as well as the precise orchestration of neuronal migration. Eph/ephrin signaling is crucial in guiding neurons and their projections during embryonic development. In adult ephrin-A2 knockout mice we consistently observed focal patches of disorganized neocortical laminar architecture, ranging in severity from reduced neuronal density to a complete lack of neurons. Loss of ephrin-A2 in the pre-optic area of the diencephalon reduced the migration of neocortex-bound interneurons from this region. Furthermore, ephrin-A2 participates in the creation of excitatory neurons by inhibiting apical progenitor proliferation in the ventricular zone, with the disruption of ephrin-A2 signaling in these cells recapitulating the abnormal neocortex observed in the knockout. The disturbance to the architecture of the neocortex observed following deletion of ephrin-A2 signaling shares many similarities with defects found in the neocortex of children diagnosed with autism spectrum disorder.

    Original languageEnglish
    Article number11813
    JournalScientific Reports
    Volume7
    Issue number1
    DOIs
    Publication statusPublished - 1 Dec 2017

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