FoxJ1 regulates spinal cord development and is required for the maintenance of spinal cord stem cell potential

Exp Cell Res. 2018 Jul 1;368(1):84-100. doi: 10.1016/j.yexcr.2018.04.017. Epub 2018 Apr 22.

Abstract

Development of the spinal cord requires dynamic and tightly controlled expression of numerous transcription factors. Forkhead Box protein J1 (FoxJ1) is a transcription factor involved in ciliogenesis and is specifically expressed in ependymal cells (ECs) in the adult central nervous system. However, using FoxJ1 fate-mapping mouse lines, we observed that FoxJ1 is also transiently expressed by the progenitors of other neural subtypes during development. Moreover, using a knock-in mouse line, we discovered that FoxJ1 is essential for embryonic progenitors to follow a normal developmental trajectory. FoxJ1 loss perturbed embryonic progenitor proliferation and cell fate determination, and resulted in formation of adult ECs having impaired stem cell potential and an inability to respond to spinal cord injury in both male and female animals. Thus, our study uncovers unexpected developmental functions of FoxJ1 in cell fate determination of subsets of neural cells and suggests that FoxJ1 is critical for maintaining the stem cell potential of ECs into adulthood.

Keywords: Astrocyte subtypes; Differentiation; Ependymal cells; Neural progenitors; Self-renewal; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Ependyma / metabolism
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation / genetics*
  • Male
  • Mice
  • Organogenesis / physiology
  • Spinal Cord / metabolism
  • Spinal Cord Injuries / metabolism
  • Stem Cells / cytology*

Substances

  • FOXJ1 protein, mouse
  • Forkhead Transcription Factors

Grant support