Lhx6 Directly Regulates Arx and CXCR7 to Determine Cortical Interneuron Fate and Laminar Position
Copyright policy )Lhx6 Directly Regulates Arx and CXCR7 to Determine Cortical Interneuron Fate and Laminar Position
Cortical GABAergic interneurons have essential roles for information processing and their dysfunction is implicated in neuropsychiatric disorders. Transcriptional codes are elucidating mechanisms of interneuron specification in the MGE (a subcortical progenitor zone), which regulate their migration, integration, and function within cortical circuitry. Lhx6, a LIM-homeodomain transcription factor, is essential for specification of MGE-derived somatostatin and parvalbumin interneurons. Here, we demonstrate that some Lhx6⁻/⁻ MGE cells acquire a CGE-like fate. Using an in vivo MGE complementation/transplantation assay, we show that Lhx6-regulated genes Arx and CXCR7 rescue divergent aspects of Lhx6⁻/⁻ cell-fate and laminar mutant phenotypes and provide insight into a neonatal role for CXCR7 in MGE-derived interneuron lamination. Finally, Lhx6 directly binds in vivo to an Arx enhancer and to an intronic CXCR7 enhancer that remains active in mature interneurons. These data define the molecular identity of Lhx6 mutants and introduce technologies to test mechanisms in GABAergic interneuron differentiation.
- Kyoto University Japan
- UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- University of California System United States
- Fudan University China (People's Republic of)
- University of California, San Francisco United States
1.1 Normal biological development and functioning, Neuroscience(all), Chemokine CXCL1, LIM-Homeodomain Proteins, Action Potentials, Mice, Transgenic, Nerve Tissue Proteins, In Vitro Techniques, Transgenic, Mice, Underpinning research, Cell Movement, Interneurons, Receptors, Genetics, Psychology, Animals, Humans, Developmental, CXCR, Cerebral Cortex, Homeodomain Proteins, Receptors, CXCR, Neurology & Neurosurgery, Biomedical and Clinical Sciences, Mammalian, Stem Cells, Neurosciences, Age Factors, Gene Expression Regulation, Developmental, Embryo, Mammalian, Luminescent Proteins, HEK293 Cells, Gene Expression Regulation, Embryo, Biological psychology, Cognitive Sciences, Biotechnology, Transcription Factors, Stem Cell Transplantation
1.1 Normal biological development and functioning, Neuroscience(all), Chemokine CXCL1, LIM-Homeodomain Proteins, Action Potentials, Mice, Transgenic, Nerve Tissue Proteins, In Vitro Techniques, Transgenic, Mice, Underpinning research, Cell Movement, Interneurons, Receptors, Genetics, Psychology, Animals, Humans, Developmental, CXCR, Cerebral Cortex, Homeodomain Proteins, Receptors, CXCR, Neurology & Neurosurgery, Biomedical and Clinical Sciences, Mammalian, Stem Cells, Neurosciences, Age Factors, Gene Expression Regulation, Developmental, Embryo, Mammalian, Luminescent Proteins, HEK293 Cells, Gene Expression Regulation, Embryo, Biological psychology, Cognitive Sciences, Biotechnology, Transcription Factors, Stem Cell Transplantation
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