Dlx transcription factors promote migration through repression of axon and dendrite growth

Neuron. 2007 Jun 21;54(6):873-88. doi: 10.1016/j.neuron.2007.05.024.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Axons / drug effects
  • Axons / physiology*
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Dendrites / drug effects
  • Dendrites / physiology*
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Green Fluorescent Proteins / biosynthesis
  • Homeodomain Proteins / classification
  • Homeodomain Proteins / physiology*
  • In Vitro Techniques
  • Interneurons / cytology*
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Mice
  • Mice, Transgenic
  • Microarray Analysis / methods
  • Pregnancy
  • Protein-Serine-Threonine Kinases / metabolism
  • Pyramidal Cells / cytology
  • Pyramidal Cells / physiology
  • RNA, Small Interfering / pharmacology
  • Transcription Factors / classification
  • Transcription Factors / deficiency
  • Transcription Factors / physiology*
  • Transfection / methods
  • p21-Activated Kinases
  • rho GTP-Binding Proteins / metabolism

Substances

  • Distal-less homeobox proteins
  • Homeodomain Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • Green Fluorescent Proteins
  • Pak3 protein, mouse
  • Protein-Serine-Threonine Kinases
  • p21-Activated Kinases
  • rho GTP-Binding Proteins