The Microtubule Regulator NEK7 Coordinates the Wiring of Cortical Parvalbumin Interneurons

Antonio Jesús Hinojosa,Rubén Deogracias,Beatriz Rico

doi:10.1016/j.celrep.2018.06.115

Antonio Jesús Hinojosa, Rubén Deogracias + Show 1 more

Open Access

https://doi.org/10.1016/j.celrep.2018.06.115

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Journal: Cell Reports	Publication Date: Jul 1, 2018
Citations: 19	License type: cc-by

Affiliation: King's College London, Instituto de Neurociencias

Abstract

SummaryFunctional networks in the mammalian cerebral cortex rely on the interaction between glutamatergic pyramidal cells and GABAergic interneurons. Both neuronal populations exhibit an extraordinary divergence in morphology and targeting areas, which ultimately dictate their precise function in cortical circuits. How these prominent morphological differences arise during development is not well understood. Here, we conducted a high-throughput screen for genes differentially expressed by pyramidal cells and interneurons during cortical wiring. We found that NEK7, a kinase involved in microtubule polymerization, is mostly expressed in parvalbumin (PV+) interneurons at the time when they establish their connectivity. Functional experiments revealed that NEK7-deficient PV+ interneurons show altered microtubule dynamics, axon growth cone steering and reduced axon length, arbor complexity, and total number of synaptic contacts formed with pyramidal cells. Altogether, our results reveal a molecular mechanism by which the microtubule-associated kinase NEK7 regulates the wiring of PV+ interneurons.

Highlights

Identifying the mechanisms by which neurons are precisely wired in specific circuits is critical to elucidate how the extraordinary complexity of brain function emerges
Identification of Differentially Expressed Genes during the Wiring of GABAergic Interneurons Pyramidal cells and interneurons are remarkably different in morphology and synaptic targeting with distinct contributions to the cortical network
We used fluorescence-activated cell sorting (FACS) to isolate pyramidal cells and interneurons using mice reporting these populations with GFP at two different stages and subsequently carried out transcriptome analyses (Figure 1A)

Summary

Graphical Abstract

Mature cortical circuits emerge during development by the integration of two morphologically distinguished neuronal populations, pyramidal cells and interneurons. Hinojosa et al reveal a molecular program by which a microtubule-associated kinase controls the shape and wiring of cortical interneurons. Highlights d Nek is expressed by GABAergic interneurons during cortical wiring d Loss of Nek in vitro alters microtubule dynamics, axon steering, and morphology d Loss of Nek in vivo impairs the morphology and synaptic outputs of PV interneurons.

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