Extracellular Pax6 Regulates Tangential Cajal-Retzius Cell Migration in the Developing Mouse Neocortex

H Kaddour; E Coppola; A A Di Nardo; C Le Poupon; P Mailly; A Wizenmann; M Volovitch; A Prochiantz; A Pierani

doi:10.1093/cercor/bhz098

Extracellular Pax6 Regulates Tangential Cajal-Retzius Cell Migration in the Developing Mouse Neocortex

Cereb Cortex. 2020 Mar 21;30(2):465-475. doi: 10.1093/cercor/bhz098.

Authors

H Kaddour^{1

2

3

4}, E Coppola^{2

3

4}, A A Di Nardo¹, C Le Poupon¹, P Mailly⁵, A Wizenmann⁶, M Volovitch¹, A Prochiantz¹, A Pierani^{2

3

4}

Affiliations

¹ Center for Interdisciplinary Research in Biology, Centre National de la Recherche Scientifique Unité mixte de recherche 7241/Institut national de la santé et de la recherche médicale U1050, Paris Science Lettre University, Labex MemoLife, Collège de France, 11 place Marcelin Berthelot, Paris, France.
² Institut Jacques Monod, Centre National de la Recherche Scientifique Unité mixte de recherche 7592, Université Paris Diderot, Sorbonne Paris Cité, 15 Rue Hélène Brion, Paris, France.
³ Imagine Institute for Genetic Diseases, Université Paris Descartes, 24 Boulevard du Montparnasse, Paris, France.
⁴ Institute of Psychiatry and Neuroscience of Paris, Université Paris Descartes, 102-108 Rue de la Santé, Paris, France.
⁵ Center for Interdisciplinary Research in Biology, Centre National de la Recherche Scientifique, Core Facility Orion, 11 Place Marcelin Berthelot, Paris, France.
⁶ Department of Anatomy, Institute of Clinical Anatomy and Cell, University of Tübingen, Osterbergstrasse 3, Tübingen, Germany.

PMID: 31206158
DOI: 10.1093/cercor/bhz098

Abstract

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.

Keywords: Cajal–Retzius neurons; Pax6; embryonic cerebral cortex; migration; noncell autonomous.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Movement*
Mice, Inbred C57BL
Mice, Transgenic
Neocortex / growth & development*
Neurons / physiology*
PAX6 Transcription Factor / physiology*

Substances

PAX6 Transcription Factor
Pax6 protein, mouse