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.
Highlights
The mammalian neocortex processes sensory information, controls motor output, and mediates higher cognitive functions
We demonstrate that cadherin 2 (CDH2) and CDH4 cooperate to regulate radial migration in the neocortex through the engagement of catenin proteins in a process that is regulated by protein tyrosine phosphatase 1B (PTP1B)
Cadherin expression in the developing neocortex Previous studies using a dominant-negative cadherin (DN-CDH) that interferes with the function of most classical cadherins have revealed a role for cadherins in the radial migration of neocortical projection neurons (Franco et al, 2011; Gil-Sanz et al, 2013; Jossin and Cooper, 2011; Kawauchi et al, 2010)
Summary
The mammalian neocortex processes sensory information, controls motor output, and mediates higher cognitive functions. Excitatory neurons of the neocortex are largely generated in the ventricular zone (VZ) and subventricular zones (SVZ) of the dorsal pallium. From their place of birth, these neurons migrate radially to establish neocortical cell layers. Deep and upper layer neurons use distinct forms of motility to reach their final position. Neurons that will populate deep layers V and VI migrate at a time when the cortical plate (CP) is still relatively thin.
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