The Iroquois (Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron development

Summary: The Iroquois (Iro/Irx) homeobox genes encode transcription factors with fundamental roles in animal development. Despite their link to various congenital conditions in humans, our understanding of Iro/Irx gene expression, function, and regulation remains incomplete. Here, we conducted a sys...

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Main Authors: Catarina Catela, Stavroula Assimacopoulos, Yihan Chen, Konstantinos Tsioras, Weidong Feng, Paschalis Kratsios
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225004717
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author Catarina Catela
Stavroula Assimacopoulos
Yihan Chen
Konstantinos Tsioras
Weidong Feng
Paschalis Kratsios
author_facet Catarina Catela
Stavroula Assimacopoulos
Yihan Chen
Konstantinos Tsioras
Weidong Feng
Paschalis Kratsios
author_sort Catarina Catela
collection DOAJ
description Summary: The Iroquois (Iro/Irx) homeobox genes encode transcription factors with fundamental roles in animal development. Despite their link to various congenital conditions in humans, our understanding of Iro/Irx gene expression, function, and regulation remains incomplete. Here, we conducted a systematic expression analysis of all six mouse Irx genes in the embryonic spinal cord. We found that Irx1, Irx2, Irx3, Irx5, and Irx6 are expressed in specific groups of motor neurons (MNs). Further, we employed CRISPR-Cas9 gene editing to uncover essential but distinct roles for Irx2 and Irx6 in MN development. We also found that HOX proteins, which are conserved regulators of MN development across species, control Irx gene expression both in mouse and Caenorhabditis elegans MNs. Altogether, our study provides insights into Iro/Irx expression and function in the developing spinal cord and uncovers an ancient gene regulatory relationship between HOX and Iro/Irx genes.
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publishDate 2025-04-01
publisher Elsevier
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series iScience
spelling doaj-art-2a531da94e9b4989a96a233770ffb0aa2025-08-20T02:10:01ZengElsevieriScience2589-00422025-04-0128411221010.1016/j.isci.2025.112210The Iroquois (Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron developmentCatarina Catela0Stavroula Assimacopoulos1Yihan Chen2Konstantinos Tsioras3Weidong Feng4Paschalis Kratsios5Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Neuroscience Institute, University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Neuroscience Institute, University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Neuroscience Institute, University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Neuroscience Institute, University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Neuroscience Institute, University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Neuroscience Institute, University of Chicago, Chicago, IL 60637, USA; Corresponding authorSummary: The Iroquois (Iro/Irx) homeobox genes encode transcription factors with fundamental roles in animal development. Despite their link to various congenital conditions in humans, our understanding of Iro/Irx gene expression, function, and regulation remains incomplete. Here, we conducted a systematic expression analysis of all six mouse Irx genes in the embryonic spinal cord. We found that Irx1, Irx2, Irx3, Irx5, and Irx6 are expressed in specific groups of motor neurons (MNs). Further, we employed CRISPR-Cas9 gene editing to uncover essential but distinct roles for Irx2 and Irx6 in MN development. We also found that HOX proteins, which are conserved regulators of MN development across species, control Irx gene expression both in mouse and Caenorhabditis elegans MNs. Altogether, our study provides insights into Iro/Irx expression and function in the developing spinal cord and uncovers an ancient gene regulatory relationship between HOX and Iro/Irx genes.http://www.sciencedirect.com/science/article/pii/S2589004225004717Molecular biologyNeuroscience
spellingShingle Catarina Catela
Stavroula Assimacopoulos
Yihan Chen
Konstantinos Tsioras
Weidong Feng
Paschalis Kratsios
The Iroquois (Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron development
iScience
Molecular biology
Neuroscience
title The Iroquois (Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron development
title_full The Iroquois (Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron development
title_fullStr The Iroquois (Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron development
title_full_unstemmed The Iroquois (Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron development
title_short The Iroquois (Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron development
title_sort iroquois iro irx homeobox genes are conserved hox targets involved in motor neuron development
topic Molecular biology
Neuroscience
url http://www.sciencedirect.com/science/article/pii/S2589004225004717
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