Ephrin-B2 paces neuronal production in the developing neocortex

BMC Dev Biol. 2020 May 13;20(1):12. doi: 10.1186/s12861-020-00215-3.

Abstract

Background: During mammalian cerebral cortex development, different types of projection neurons are produced in a precise temporal order and in stereotypical numbers. The mechanisms regulating timely generation of neocortex projection neurons and ensuring production in sufficient numbers of each neuronal identity are only partially understood.

Results: Here, we show that ephrin-B2, a member of the Eph:ephrin cell-to-cell communication pathway, sets the neurogenic tempo in the neocortex. Indeed, conditional mutant embryos for ephrin-B2 exhibit a transient delay in neurogenesis and acute stimulation of Eph signaling by in utero injection of synthetic ephrin-B2 led to a transient increase in neuronal production. Using genetic approaches we show that ephrin-B2 acts on neural progenitors to control their differentiation in a juxtacrine manner. Unexpectedly, we observed that perinatal neuron numbers recovered following both loss and gain of ephrin-B2, highlighting the ability of neural progenitors to adapt their behavior to the state of the system in order to produce stereotypical numbers of neurons.

Conclusions: Altogether, our data uncover a role for ephrin-B2 in embryonic neurogenesis and emphasize the plasticity of neuronal production in the neocortex.

Keywords: Eph:ephrin signaling; Mouse; Neocortex; Neural progenitors; Neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Ephrin-B2 / genetics
  • Ephrin-B2 / metabolism*
  • Female
  • Fluorescent Antibody Technique
  • Male
  • Mice
  • Neocortex / cytology*
  • Neocortex / metabolism*
  • Neurogenesis / genetics
  • Neurogenesis / physiology
  • Neurons / cytology*
  • Neurons / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • Ephrin-B2