TheLhx2Transcription Factor Controls Thalamocortical Axonal Guidance by Specific Regulation of Robo1 and Robo2 Receptors
| Autor: | Sandra Peregrín, Leif Carlsson, Guillermina López-Bendito, Paula Marcos-Mondéjar, James Y. H. Li, Shubha Tole |
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| Rok vydání: | 2012 |
| Předmět: |
Neurogenesis
LIM-Homeodomain Proteins Thalamus Mice Transgenic Nerve Tissue Proteins Biology Mice 03 medical and health sciences 0302 clinical medicine ROBO1 Neural Pathways Biological neural network medicine Animals Receptors Immunologic Receptor Transcription factor 030304 developmental biology Cerebral Cortex Mice Knockout Medial geniculate nucleus Mice Inbred ICR 0303 health sciences General Neuroscience Gene Expression Regulation Developmental Articles Embryo Mammalian Axons 3. Good health medicine.anatomical_structure nervous system Cerebral cortex embryonic structures Cancer research Axon guidance Neuroscience Gene Deletion 030217 neurology & neurosurgery Signal Transduction Transcription Factors |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Journal of Neuroscience |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.5851-11.2012 |
| Popis: | The assembly of neural circuits is dependent upon the generation of specific neuronal subtypes, each subtype displaying unique properties that direct the formation of selective connections with appropriate target cells. Actions of transcription factors in neural progenitors and postmitotic cells are key regulators in this process. LIM-homeodomain transcription factors control crucial aspects of neuronal differentiation, including subtype identity and axon guidance. Nonetheless, their regulation during development is poorly understood and the identity of the downstream molecular effectors of their activity remains largely unknown. Here, we demonstrate that the Lhx2 transcription factor is dynamically regulated in distinct pools of thalamic neurons during the development of thalamocortical connectivity in mice. Indeed, overexpression of Lhx2 provokes defective thalamocortical axon guidance in vivo, while specific conditional deletion of Lhx2 in the thalamus produces topographic defects that alter projections from the medial geniculate nucleus and from the caudal ventrobasal nucleus in particular. Moreover, we demonstrate that Lhx2 influences axon guidance and the topographical sorting of axons by regulating the expression of Robo1 and Robo2 guidance receptors, which are essential for these axons to establish correct connections in the cerebral cortex. Finally, augmenting Robo1 function restores normal axon guidance in Lhx2-overexpressing neurons. By regulating axon guidance receptors, such as Robo1 and Robo2, Lhx2 differentially regulates the axon guidance program of distinct populations of thalamic neurons, thus enabling the establishment of specific neural connections. © 2012 the authors. This work was supported by grants from the Spanish Ministry of Science and Innovation (BFU2006-00408/BFI, BFU2009-08261, and Consolider CSD2007-00023). P.M.-M. was supported by a Formación de Personal Investigador Fellowship from the Spanish Ministry of Science and Innovation. |
| Databáze: | OpenAIRE |
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