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Updated: Jul 14, 2026

Ex Utero Electroporation and Organotypic Slice Cultures of Embryonic Mouse Brains for Live-Imaging of Migrating GABAergic Interneurons
Published on: April 20, 2018
Dlx transcription factors promote migration through repression of axon and dendrite growth
Inma Cobos1, Ugo Borello, John L R Rubenstein
1Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA. inma.cobos@ucsf.edu
Abstract:
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.
Insights
Dlx1/2 transcription factors are crucial for guiding immature neurons in the mouse brain. They control neurite growth and migration, ensuring proper development and positioning within the neocortex.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Dlx homeobox transcription factors are vital for GABAergic interneuron migration in the mouse telencephalon.
- The precise mechanisms governing this tangential migration process remain largely unknown.
Purpose of the Study:
- To elucidate the role of Dlx1/2 in regulating neurite growth and tangential migration of subpallial-derived interneurons.
- To identify downstream targets of Dlx1/2 involved in coordinating neurite maturation and neuronal migration.
Main Methods:
- Analysis of Dlx1/2 knockout and heterozygous mutant mice.
- Assessment of neurite outgrowth, branching, and migration patterns of interneurons.
- Genetic analysis to identify Dlx1/2 downstream effectors.
Main Results:
- Dlx1/2 deficiency leads to increased neurite length and impaired tangential migration of interneurons.
- Partial Dlx1/2 loss affects neurite morphology and neocortical laminar positioning.
- Dlx1/2 represses PAK3 activity, a key regulator of neurite growth and migration.
Conclusions:
- Dlx1/2 plays a critical role in coordinating neurite development and tangential migration of interneurons.
- Repression of PAK3 by Dlx1/2 is essential for restraining neurite growth and facilitating migration.
- These findings highlight Dlx1/2's importance in the proper formation of cortical circuitry.
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