Nests of dividing neuroblasts sustain interneuron production for the developing human brain

Science. 2022 Jan 28;375(6579):eabk2346. doi: 10.1126/science.abk2346. Epub 2022 Jan 28.

Abstract

The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mouse brain, they reform into nests containing proliferating neuroblasts that generate young neurons that migrate extensively into the mouse forebrain and mature into different subtypes of functional interneurons. Together, these results indicate that the nest organization and sustained proliferation of neuroblasts in the hMGE provide a mechanism for the extended production of interneurons for the human forebrain.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Movement
  • Cell Proliferation
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Cerebral Cortex / growth & development
  • GABAergic Neurons / cytology
  • GABAergic Neurons / physiology
  • Gene Expression Profiling
  • Gestational Age
  • Humans
  • Interneurons / cytology
  • Interneurons / physiology*
  • Median Eminence / cytology
  • Median Eminence / embryology*
  • Median Eminence / growth & development
  • Mice
  • Neural Stem Cells / physiology*
  • Neural Stem Cells / transplantation
  • Neurogenesis*
  • Prosencephalon / cytology*
  • Prosencephalon / embryology
  • Prosencephalon / growth & development
  • Transplantation, Heterologous