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Crim1 and Kelch-like 14 exert complementary dual-directional developmental control over segmentally specific corticospinal axon projection targeting

The cerebral cortex executes highly skilled movement, necessitating that it connects accurately with specific brainstem and spinal motor circuitry. Corticospinal neurons (CSN) must correctly target specific spinal segments, but the basis for this targeting remains unknown. In the accompanying report...

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Detalles Bibliográficos
Autores principales: Sahni, Vibhu, Itoh, Yasuhiro, Shnider, Sara J., Macklis, Jeffrey D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8697027/
https://www.ncbi.nlm.nih.gov/pubmed/34686337
http://dx.doi.org/10.1016/j.celrep.2021.109842
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author Sahni, Vibhu
Itoh, Yasuhiro
Shnider, Sara J.
Macklis, Jeffrey D.
author_facet Sahni, Vibhu
Itoh, Yasuhiro
Shnider, Sara J.
Macklis, Jeffrey D.
author_sort Sahni, Vibhu
collection PubMed
description The cerebral cortex executes highly skilled movement, necessitating that it connects accurately with specific brainstem and spinal motor circuitry. Corticospinal neurons (CSN) must correctly target specific spinal segments, but the basis for this targeting remains unknown. In the accompanying report, we show that segmentally distinct CSN subpopulations are molecularly distinct from early development, identifying candidate molecular controls over segmentally specific axon targeting. Here, we functionally investigate two of these candidate molecular controls, Crim1 and Kelch-like 14 (Klhl14), identifying their critical roles in directing CSN axons to appropriate spinal segmental levels in the white matter prior to axon collateralization. Crim1 and Klhl14 are specifically expressed by distinct CSN subpopulations and regulate their differental white matter projection targeting—Crim1 directs thoracolumbar axon extension, while Klhl14 limits axon extension to bulbar-cervical segments. These molecular regulators of descending spinal projections constitute the first stages of a dual-directional set of complementary controls over CSN diversity for segmentally and functionally distinct circuitry.
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spelling pubmed-86970272021-12-23 Crim1 and Kelch-like 14 exert complementary dual-directional developmental control over segmentally specific corticospinal axon projection targeting Sahni, Vibhu Itoh, Yasuhiro Shnider, Sara J. Macklis, Jeffrey D. Cell Rep Article The cerebral cortex executes highly skilled movement, necessitating that it connects accurately with specific brainstem and spinal motor circuitry. Corticospinal neurons (CSN) must correctly target specific spinal segments, but the basis for this targeting remains unknown. In the accompanying report, we show that segmentally distinct CSN subpopulations are molecularly distinct from early development, identifying candidate molecular controls over segmentally specific axon targeting. Here, we functionally investigate two of these candidate molecular controls, Crim1 and Kelch-like 14 (Klhl14), identifying their critical roles in directing CSN axons to appropriate spinal segmental levels in the white matter prior to axon collateralization. Crim1 and Klhl14 are specifically expressed by distinct CSN subpopulations and regulate their differental white matter projection targeting—Crim1 directs thoracolumbar axon extension, while Klhl14 limits axon extension to bulbar-cervical segments. These molecular regulators of descending spinal projections constitute the first stages of a dual-directional set of complementary controls over CSN diversity for segmentally and functionally distinct circuitry. 2021-10-19 /pmc/articles/PMC8697027/ /pubmed/34686337 http://dx.doi.org/10.1016/j.celrep.2021.109842 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license.
spellingShingle Article
Sahni, Vibhu
Itoh, Yasuhiro
Shnider, Sara J.
Macklis, Jeffrey D.
Crim1 and Kelch-like 14 exert complementary dual-directional developmental control over segmentally specific corticospinal axon projection targeting
title Crim1 and Kelch-like 14 exert complementary dual-directional developmental control over segmentally specific corticospinal axon projection targeting
title_full Crim1 and Kelch-like 14 exert complementary dual-directional developmental control over segmentally specific corticospinal axon projection targeting
title_fullStr Crim1 and Kelch-like 14 exert complementary dual-directional developmental control over segmentally specific corticospinal axon projection targeting
title_full_unstemmed Crim1 and Kelch-like 14 exert complementary dual-directional developmental control over segmentally specific corticospinal axon projection targeting
title_short Crim1 and Kelch-like 14 exert complementary dual-directional developmental control over segmentally specific corticospinal axon projection targeting
title_sort crim1 and kelch-like 14 exert complementary dual-directional developmental control over segmentally specific corticospinal axon projection targeting
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8697027/
https://www.ncbi.nlm.nih.gov/pubmed/34686337
http://dx.doi.org/10.1016/j.celrep.2021.109842
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