ALK4 coordinates extracellular and intrinsic signals to regulate development of cortical somatostatin interneurons. Academic Article uri icon

Overview

abstract

  • Although the role of transcription factors in fate specification of cortical interneurons is well established, how these interact with extracellular signals to regulate interneuron development is poorly understood. Here we show that the activin receptor ALK4 is a key regulator of the specification of somatostatin interneurons. Mice lacking ALK4 in GABAergic neurons of the medial ganglionic eminence (MGE) showed marked deficits in distinct subpopulations of somatostatin interneurons from early postnatal stages of cortical development. Specific losses were observed among distinct subtypes of somatostatin+/Reelin+ double-positive cells, including Hpse+ layer IV cells targeting parvalbumin+ interneurons, leading to quantitative alterations in the inhibitory circuitry of this layer. Activin-mediated ALK4 signaling in MGE cells induced interaction of Smad2 with SATB1, a transcription factor critical for somatostatin interneuron development, and promoted SATB1 nuclear translocation and repositioning within the somatostatin gene promoter. These results indicate that intrinsic transcriptional programs interact with extracellular signals present in the environment of MGE cells to regulate cortical interneuron specification.

publication date

  • January 6, 2020

Research

keywords

  • Activin Receptors, Type I
  • Cerebral Cortex
  • GABAergic Neurons
  • Interneurons
  • Median Eminence
  • Neurogenesis
  • Somatostatin

Identity

PubMed Central ID

  • PMC7039195

Scopus Document Identifier

  • 85076331376

Digital Object Identifier (DOI)

  • 10.1126/science.aaa1934

PubMed ID

  • 31676717

Additional Document Info

volume

  • 219

issue

  • 1