Dlx transcription factors promote migration through repression of axon and dendrite growth.
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.
Cobos
Inma
I
Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA. inma.cobos@ucsf.edu
Borello
Ugo
U
Rubenstein
John L R
JL
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D004622:Embryo, Mammalian; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000145:classification / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis / Q000379:methods; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D014157:Transcription Factors / Q000145:classification / Q000172:deficiency / Q000502:physiology*; D014162:Transfection / Q000379:methods; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins / Q000378:metabolism
C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C515912:Pak3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins