Dlx transcription factors promote migration through repression of axon and dendrite growth
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In the mouse telencephalon, Dlx homeobox transcription factors are essential for the tangential migration of subpallial-derived GABAergic interneurons to neocortex. However, the mechanisms underlying this process are poorly understood. Here, we demonstrate that Dlx1/2 has a central role in restraining neurite growth of subpallial-derived immature interneurons at a stage when they migrate tangentially to cortex. In Dlx1-/-;Dlx2-/- mutants, neurite length is increased and cells fail to migrate. In Dlx1-/-;Dlx2+/- mutants, while the tangential migration of immature interneurons appears normal, they develop dendritic and axonal processes with increased length and decreased branching, and have deficits in their neocortical laminar positions. Thus, Dlx1/2 is required for coordinating programs of neurite maturation and migration. In this regard, we provide genetic evidence that in immature interneurons Dlx1/2 repression of the p21-activated serine/threonine kinase PAK3, a downstream effector of the Rho family of GTPases, is critical in restraining neurite growth and promoting tangential migration.
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Dlx1 is required for expression of Elmo1, a Rac activator that regulates migration of some interneuron types.
“Dlx1 is in turn required for expression of Elmo1 (Cobos et al., 2007), a gene encoding a Rac activator protein that regulates the migration of some types of interneuron (De Marco García et al., 2011).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Cobos et al., 2007
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- Authors
- Cobos, I., Borello, U., & Rubenstein, J. L. R.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Cobos, Inma
- Rubenstein, John L.R.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 54
- Issue
- 6
- Pages
- 873-888
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4921237
- OpenAlex
- W2060612598
- Cited by
- 246
- References
- 79
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 7 · 2021: 11 · 2020: 16 · 2019: 13 · 2018: 11 · 2017: 5 · 2016: 10 · 2015: 7 · 2014: 13 · 2013: 27 · 2012: 15
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2274 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institute of Mental Health (K05 MH065670, RO1 MH49428)
- Human Frontier Science Program
- Autism Speaks
- Larry L. Hillblom Foundation
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- DLX1, Dlx2, homeodomain transcription factor, tangential migration, GABAergic interneurons, subpallium, neocortex, neurite outgrowth, axon growth, dendritic growth, PAK3, Rho GTPases, cortical lamination, neuronal migration
- MeSH terms
- Animals, Animals, Newborn, Axons, Cell Movement, Cells, Cultured, Cerebral Cortex, Dendrites, Embryo, Mammalian, Female, Gene Expression Regulation, Interneurons, Mice, Transgenic, Pregnancy, Transcription Factors, Transfection, Protein Serine-Threonine Kinases, Pyramidal Cells, Homeodomain Proteins, rho GTP-Binding Proteins, RNA, Small Interfering, Microarray Analysis, Green Fluorescent Proteins, Mice, p21-Activated Kinases, In Vitro Techniques
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