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Lhx4 surpasses its paralog Lhx3 in promoting the differentiation of spinal V2a interneurons.
Renaux, Estelle; Baudouin, Charlotte; Marchese, Damien; Clovis, Yoanne; Lee, Soo-Kyung; Gofflot, Françoise; Rezsohazy, René; Clotman, Frédéric.
Afiliación
  • Renaux E; Université catholique de Louvain, Louvain Institute of Biomolecular Science and Technology, Animal Molecular and Cellular Biology, Louvain-la-Neuve, 1348, Belgium.
  • Baudouin C; Université catholique de Louvain, Institute of Neuroscience, Laboratory of Neural Differentiation, Brussels, 1200, Belgium.
  • Marchese D; Université catholique de Louvain, Institute of Neuroscience, Laboratory of Neural Differentiation, Brussels, 1200, Belgium.
  • Clovis Y; Université catholique de Louvain, Louvain Institute of Biomolecular Science and Technology, Animal Molecular and Cellular Biology, Louvain-la-Neuve, 1348, Belgium.
  • Lee SK; Pediatric Neuroscience Research Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, Portland, OR, 97239, USA.
  • Gofflot F; Pediatric Neuroscience Research Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, Portland, OR, 97239, USA.
  • Rezsohazy R; Department of Biological Sciences, University at Buffalo, Buffalo, NY, 14260, USA.
  • Clotman F; Université catholique de Louvain, Louvain Institute of Biomolecular Science and Technology, Animal Molecular and Cellular Biology, Louvain-la-Neuve, 1348, Belgium.
Cell Mol Life Sci ; 81(1): 286, 2024 Jul 06.
Article en En | MEDLINE | ID: mdl-38970652
ABSTRACT
Paralog factors are considered to ensure the robustness of biological processes by providing redundant activity in cells where they are co-expressed. However, the specific contribution of each factor is frequently underestimated. In the developing spinal cord, multiple families of transcription factors successively contribute to differentiate an initially homogenous population of neural progenitors into a myriad of neuronal subsets with distinct molecular, morphological, and functional characteristics. The LIM-homeodomain transcription factors Lhx3, Lhx4, Isl1 and Isl2 promote the segregation and differentiation of spinal motor neurons and V2 interneurons. Based on their high sequence identity and their similar distribution, the Lhx3 and Lhx4 paralogs are considered to contribute similarly to these processes. However, the specific contribution of Lhx4 has never been studied. Here, we provide evidence that Lhx3 and Lhx4 are present in the same cell populations during spinal cord development. Similarly to Lhx3, Lhx4 can form multiproteic complexes with Isl1 or Isl2 and the nuclear LIM interactor NLI. Lhx4 can stimulate a V2-specific enhancer more efficiently than Lhx3 and surpasses Lhx3 in promoting the differentiation of V2a interneurons in chicken embryo electroporation experiments. Finally, Lhx4 inactivation in mice results in alterations of differentiation of the V2a subpopulation, but not of motor neuron production, suggesting that Lhx4 plays unique roles in V2a differentiation that are not compensated by the presence of Lhx3. Thus, Lhx4 could be the major LIM-HD factor involved in V2a interneuron differentiation during spinal cord development and should be considered for in vitro differentiation of spinal neuronal populations.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Médula Espinal / Factores de Transcripción / Diferenciación Celular / Proteínas con Homeodominio LIM / Interneuronas Límite: Animals / Humans Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Bélgica

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Médula Espinal / Factores de Transcripción / Diferenciación Celular / Proteínas con Homeodominio LIM / Interneuronas Límite: Animals / Humans Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Bélgica