ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons

LIM-homeodomain (HD) transcription factors form a multimeric complex and assign neuronal subtype identities, as demonstrated by the hexameric ISL1-LHX3 complex which gives rise to somatic motor (SM) neurons. However, the roles of combinatorial LIM code in motor neuron diversification and their subse...

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Main Authors: Kim, Kyung-Tai, Kim, Namhee, Kim, Hwan-Ki, Lee, Hojae, Gruner, Hannah N., Gergics, Peter, Park, Chungoo, Mastick, Grant S., Park, Hae-Chul, Song, Mi-Ryoung
Format: Online
Language:English
Published: Nature Publishing Group 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098159/
id pubmed-5098159
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spelling pubmed-50981592016-11-10 ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons Kim, Kyung-Tai Kim, Namhee Kim, Hwan-Ki Lee, Hojae Gruner, Hannah N. Gergics, Peter Park, Chungoo Mastick, Grant S. Park, Hae-Chul Song, Mi-Ryoung Article LIM-homeodomain (HD) transcription factors form a multimeric complex and assign neuronal subtype identities, as demonstrated by the hexameric ISL1-LHX3 complex which gives rise to somatic motor (SM) neurons. However, the roles of combinatorial LIM code in motor neuron diversification and their subsequent differentiation is much less well understood. In the present study, we demonstrate that the ISL1 controls postmitotic cranial branchiomotor (BM) neurons including the positioning of the cell bodies and peripheral axon pathfinding. Unlike SM neurons, which transform into interneurons, BM neurons are normal in number and in marker expression in Isl1 mutant mice. Nevertheless, the movement of trigeminal and facial BM somata is stalled, and their peripheral axons are fewer or misrouted, with ectopic branches. Among genes whose expression level changes in previous ChIP-seq and microarray analyses in Isl1-deficient cell lines, we found that Slit2 transcript was almost absent from BM neurons of Isl1 mutants. Both ISL1-LHX3 and ISL1-LHX4 bound to the Slit2 enhancer and drove endogenous Slit2 expression in SM and BM neurons. Our findings suggest that combinations of ISL1 and LHX factors establish cell-type specificity and functional diversity in terms of motor neuron identities and/or axon development. Nature Publishing Group 2016-11-07 /pmc/articles/PMC5098159/ /pubmed/27819291 http://dx.doi.org/10.1038/srep36491 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Kim, Kyung-Tai
Kim, Namhee
Kim, Hwan-Ki
Lee, Hojae
Gruner, Hannah N.
Gergics, Peter
Park, Chungoo
Mastick, Grant S.
Park, Hae-Chul
Song, Mi-Ryoung
spellingShingle Kim, Kyung-Tai
Kim, Namhee
Kim, Hwan-Ki
Lee, Hojae
Gruner, Hannah N.
Gergics, Peter
Park, Chungoo
Mastick, Grant S.
Park, Hae-Chul
Song, Mi-Ryoung
ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons
author_facet Kim, Kyung-Tai
Kim, Namhee
Kim, Hwan-Ki
Lee, Hojae
Gruner, Hannah N.
Gergics, Peter
Park, Chungoo
Mastick, Grant S.
Park, Hae-Chul
Song, Mi-Ryoung
author_sort Kim, Kyung-Tai
title ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons
title_short ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons
title_full ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons
title_fullStr ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons
title_full_unstemmed ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons
title_sort isl1-based lim complexes control slit2 transcription in developing cranial motor neurons
description LIM-homeodomain (HD) transcription factors form a multimeric complex and assign neuronal subtype identities, as demonstrated by the hexameric ISL1-LHX3 complex which gives rise to somatic motor (SM) neurons. However, the roles of combinatorial LIM code in motor neuron diversification and their subsequent differentiation is much less well understood. In the present study, we demonstrate that the ISL1 controls postmitotic cranial branchiomotor (BM) neurons including the positioning of the cell bodies and peripheral axon pathfinding. Unlike SM neurons, which transform into interneurons, BM neurons are normal in number and in marker expression in Isl1 mutant mice. Nevertheless, the movement of trigeminal and facial BM somata is stalled, and their peripheral axons are fewer or misrouted, with ectopic branches. Among genes whose expression level changes in previous ChIP-seq and microarray analyses in Isl1-deficient cell lines, we found that Slit2 transcript was almost absent from BM neurons of Isl1 mutants. Both ISL1-LHX3 and ISL1-LHX4 bound to the Slit2 enhancer and drove endogenous Slit2 expression in SM and BM neurons. Our findings suggest that combinations of ISL1 and LHX factors establish cell-type specificity and functional diversity in terms of motor neuron identities and/or axon development.
publisher Nature Publishing Group
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098159/
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