Lamin B1 levels modulate differentiation into neurons during embryonic corticogenesis

Sci Rep. 2017 Jul 7;7(1):4897. doi: 10.1038/s41598-017-05078-6.


Lamin B1, a key component of the nuclear lamina, plays an important role in brain development. Ablation of endogenous Lamin B1 (Lmnb1) in the mouse strongly impairs embryonic brain development and corticogenesis. However, the mechanisms underlying these neurodevelopmental effects are unknown. Here, we report that Lamin B1 levels modulate the differentiation of murine neural stem cells (NSCs) into neurons and astroglial-like cells. In vitro, endogenous Lmnb1 depletion favors NSC differentiation into glial fibrillar acidic protein (GFAP)-immunoreactive cells over neurons, while overexpression of human Lamin B1 (LMNB1) increases the proportion of neurons. In Lmnb1-null embryos, neurogenesis is reduced, while in vivo Lmnb1 silencing in mouse embryonic brain by in utero electroporation of a specific Lmnb1 sh-RNA results in aberrant cortical positioning of neurons and increased expression of the astrocytic marker GFAP in the cortex of 7-day old pups. Together, these results indicate that finely tuned levels of Lamin B1 are required for NSC differentiation into neurons, proper expression of the astrocytic marker GFAP and corticogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Cell Differentiation
  • Cerebral Cortex / cytology
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / metabolism*
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental
  • Glial Fibrillary Acidic Protein / genetics*
  • Glial Fibrillary Acidic Protein / metabolism
  • Lamin Type B / antagonists & inhibitors
  • Lamin Type B / genetics*
  • Lamin Type B / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurogenesis / genetics*
  • Neurons / cytology
  • Neurons / metabolism*
  • Pregnancy
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction


  • Glial Fibrillary Acidic Protein
  • Lamin Type B
  • RNA, Small Interfering
  • glial fibrillary astrocytic protein, mouse
  • lamin B1