English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

FLRT2 and FLRT3 Cooperate in Maintaining the Tangential Migratory Streams of Cortical Interneurons during Development

MPS-Authors
/persons/resource/persons39214

del Toro,  Daniel
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;

/persons/resource/persons38927

Klein,  Rüdiger
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Fleitas, C., Marfull-Oromi, P., Chauhan, D., del Toro, D., Peguera, B., Zammou, B., et al. (2021). FLRT2 and FLRT3 Cooperate in Maintaining the Tangential Migratory Streams of Cortical Interneurons during Development. The Journal of Neuroscience, 41(35), 7350-7362. doi:10.1523/JNEUROSCI.0380-20.2021.


Cite as: http://hdl.handle.net/21.11116/0000-0009-447C-0
Abstract
Neuron migration is a hallmark of nervous system development that allows gathering of neurons from different ori-gins for assembling of functional neuronal circuits. Cortical inhibitory interneurons arise in the ventral telencephalon and migrate tangentially forming three transient migratory streams in the cortex before reaching the final laminar destination. Although migration defects lead to the disruption of inhibitory circuits and are linked to aspects of psychiatric disorders such as au-tism and schizophrenia, the molecular mechanisms controlling cortical interneuron development and final layer positioning are incompletely understood. Here, we show that mouse embryos with a double deletion of FLRT2 and FLRT3 genes encoding cell adhe-sion molecules exhibit an abnormal distribution of interneurons within the streams during development, which in turn, affect the layering of somatostatin1 interneurons postnatally. Mechanistically, FLRT2 and FLRT3 proteins act in a noncell-autonomous manner, possibly through a repulsive mechanism. In support of such a conclusion, double knockouts deficient in the repulsive receptors for FLRTs, Unc5B and Unc5D, also display interneuron defects during development, similar to the FLRT2/FLRT3 mutants. Moreover, FLRT proteins are chemorepellent ligands for developing interneurons in vitro, an effect that is in part dependent on FLRT-Unc5 interaction. Together, we propose that FLRTs act through Unc5 receptors to control cortical interneuron distribution in a mechanism that involves cell repulsion.