Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants
| Autor: | Melissa Dela Cuesta, Heiner Westphal, Yangu Zhao, Pierre Flandin, Jason E. Long, John L.R. Rubenstein |
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| Rok vydání: | 2008 |
| Předmět: |
Telencephalon
genetic structures Interneuron LIM-Homeodomain Proteins Hippocampus Mice Inbred Strains Neocortex Nerve Tissue Proteins Hippocampal formation Article Interneuron migration Mice Cell Movement Interneurons medicine Animals Cerebral Cortex Homeodomain Proteins NPAS1 biology musculoskeletal neural and ocular physiology General Neuroscience fungi Cell Differentiation Embryo Mammalian Corpus Striatum medicine.anatomical_structure Animals Newborn nervous system Mutation biology.protein Homeobox Neuroscience Parvalbumin Transcription Factors |
| Zdroj: | The Journal of Comparative Neurology. 510:79-99 |
| ISSN: | 0021-9967 |
| Popis: | Here we analyze the role of the Lhx6 lim-homeobox transcription factor in regulating the development of subsets of neocortical, hippocampal, and striatal interneurons. An Lhx6 loss-of-function allele, which expresses placental alkaline phosphatase (PLAP), allowed analysis of the development and fate of Lhx6-expressing interneurons in mice lacking this homeobox transcription factor. There are Lhx6+;Dlx+ and Lhx6-;Dlx+ subtypes of tangentially migrating interneurons. Most interneurons in Lhx6(PLAP/PLAP) mutants migrate to the cortex, although less efficiently, and exhibit defects in populating the marginal zone and superficial parts of the neocortical plate. By contrast, migration to superficial parts of the hippocampus is not seriously affected. Furthermore, whereas parvalbumin+ and somatostatin+ interneurons do not differentiate, NPY+ interneurons are present; we suggest that these NPY+ interneurons are derived from the Lhx6-;Dlx+ subtype. Striatal interneurons show deficits distinct from pallial interneurons, including a reduction in the NPY+ subtype. We provide evidence that Lhx6 mediates these effects through promoting expression of receptors that regulate interneuron migration (ErbB4, CXCR4, and CXCR7), and through promoting the expression of transcription factors either known (Arx) or implicated (bMaf, Cux2, and NPAS1) in controlling interneuron development. |
| Databáze: | OpenAIRE |
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