Cadherin 2/4 signaling via PTP1B and catenins is crucial for nucleokinesis during radial neuronal migration in the neocortex

Isabel Martinez-Garay, Cristina Gil-Sanz, Santos J. Franco, Ana Espinosa, Zoltán Molnár, Ulrich Mueller

Research output: Contribution to journalArticlepeer-review

Abstract

Cadherins are crucial for the radial migration of excitatory projection neurons into the developing neocortical wall. However, the specific cadherins and the signaling pathways that regulate radial migration are not well understood. Here, we show that cadherin 2 (CDH2) and CDH4 cooperate to regulate radial migration in mouse brain via the protein tyrosine phosphatase 1B (PTP1B) and α- and β-catenins. Surprisingly, perturbation of cadherin-mediated signaling does not affect the formation and extension of leading processes of migrating neocortical neurons. Instead, movement of the cell body and nucleus (nucleokinesis) is disrupted. This defect is partially rescued by overexpression of LIS1, a microtubule-associated protein that has previously been shown to regulate nucleokinesis. Taken together, our findings indicate that cadherin-mediated signaling to the cytoskeleton is crucial for nucleokinesis of neocortical projection neurons during their radial migration.

Original languageEnglish (US)
Pages (from-to)2121-2134
Number of pages14
JournalDevelopment (Cambridge)
Volume143
Issue number12
DOIs
StatePublished - Jun 15 2016
Externally publishedYes

Keywords

  • CDH2
  • Cadherin
  • Catenin
  • LIS1
  • Mouse
  • Nucleokinesis
  • Radial migration

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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