Journal
CEREBRAL CORTEX
Volume 30, Issue 2, Pages 465-475Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhz098
Keywords
Cajal-Retzius neurons; embryonic cerebral cortex; migration; noncell autonomous; Pax6
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Funding
- Agence National de la Recherche (ANR)-Ministry of Science and Technology (MOST) Bilateral Accord [ANR-13-ISV2-0001]
- European Research Council (ERC) Advanced Grant HOMEOSIGN [339379]
- ANR [ANR-2011-BSV4-023-01, ANR-15-CE16-0003-01]
- Fondation Recherche Medicale (FRM) [Equipe FRM DEQ20130326521]
- European Research Council (ERC) [339379] Funding Source: European Research Council (ERC)
- Agence Nationale de la Recherche (ANR) [ANR-15-CE16-0003] Funding Source: Agence Nationale de la Recherche (ANR)
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The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct noncell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 noncell autonomous activity on the migration of cortical hem- and septum-derived Cajal-Retzius (CR) neurons by live imaging of flat mount developing cerebral cortices. Blocking extracellular Pax6 disrupts tangential CR cell migration patterns by decreasing the distance traveled and changing both directionality and depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances contact repulsion in medial regions yet reduces it in lateral regions. This study demonstrates that secreted Pax6 controls neuronal migration and distribution and suggests that it acts as a bona fide morphogen at an early stage of cerebral cortex development.
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