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Reelin, Rap1 and N-cadherin orient the migration of multipolar neurons in the developing neocortex.
Nat Neurosci. 2011 Jun; 14(6):697-703
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07 Jul 2011
New Finding
DOI: 10.3410/f.11661956.12854058
This study characterises a novel signalling pathway that specifically regulates the transition of pyramidal neurons from multipolar to radial migration in the developing neocortex, a process that is crucial for correct cortical layering to take place.
In a series of in vivo gain- and loss-of-function...Continue reading
In a series of in vivo gain- and loss-of-function...Continue reading
This study characterises a novel signalling pathway that specifically regulates the transition of pyramidal neurons from multipolar to radial migration in the developing neocortex, a process that is crucial for correct cortical layering to take place.
In a series of in vivo gain- and loss-of-function experiments, this work demonstrates that the extracellular signal Reelin, mediated by its receptor very low density lipoprotein receptor (VLDLR), can regulate the intracellular activation of the small GTPase protein Rap1, which can in turn regulate cell membrane localisation of N-cadherin (N-Cad).
Activation of this signalling pathway can specifically influence the morphology of later-born cortical neurons in a cell-autonomous fashion, regulating their switch from multipolar to bipolar morphology, thus allowing subsequent radial migration into the cortical plate to take place. The authors demonstrate that inhibition of either VLDLR, Rap1 or N-Cad signalling is sufficient to stall neuronal migration within the intermediate zone of the neocortex such that affected neurons fail to reach the cortical plate. Importantly, this study sheds new light on how Reelin signalling may influence cortical development by regulating cell morphology and migration to the correct cortical layer.
In a series of in vivo gain- and loss-of-function experiments, this work demonstrates that the extracellular signal Reelin, mediated by its receptor very low density lipoprotein receptor (VLDLR), can regulate the intracellular activation of the small GTPase protein Rap1, which can in turn regulate cell membrane localisation of N-cadherin (N-Cad).
Activation of this signalling pathway can specifically influence the morphology of later-born cortical neurons in a cell-autonomous fashion, regulating their switch from multipolar to bipolar morphology, thus allowing subsequent radial migration into the cortical plate to take place. The authors demonstrate that inhibition of either VLDLR, Rap1 or N-Cad signalling is sufficient to stall neuronal migration within the intermediate zone of the neocortex such that affected neurons fail to reach the cortical plate. Importantly, this study sheds new light on how Reelin signalling may influence cortical development by regulating cell morphology and migration to the correct cortical layer.
Disclosures
None declared
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Richards L and Gobius I: F1000Prime Recommendation of [Jossin Y and Cooper JA, Nat Neurosci 2011, 14(6):697-703]. In F1000Prime, 07 Jul 2011; DOI: 10.3410/f.11661956.12854058. F1000Prime.com/11661956#eval12854058
F1000Prime Recommendations, Dissents and Comments for [Jossin Y and Cooper JA, Nat Neurosci 2011, 14(6):697-703]. In F1000Prime, 24 May 2013; F1000Prime.com/11661956
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Projection neurons migrate from the ventricular zone to the neocortical plate during the development of the mouse brain. Their overall movement is radial, but they become multipolar and move nonradially in the intermediate zone. Here we show that Reelin, the Rap1 GTPase and N-cadherin (NCad) are important for multipolar neurons to polarize their migration toward the cortical plate. Inhibition and rescue experiments indicated that Reelin regulates migration through Rap1 and Akt, and that the Rap1-regulated GTPases RalA, RalB, Rac1 and Cdc42 are also involved. We found that Rap1 regulated the plasma membrane localization of NCad and NCad rescued radial polarization when Rap1 was inhibited. However, inhibition of Rap1 or NCad had little effect on glia-dependent locomotion. We propose a multistep mechanism in which Reelin activates Rap1, Rap1 upregulates NCad, and NCad is needed to orient cell migration.
DOI: 10.1038/nn.2816
PMID: 21516100
