Concise review: Fragile X proteins in stem cell maintenance and differentiation

Stem Cells. 2014 Jul;32(7):1724-33. doi: 10.1002/stem.1698.


Fragile X syndrome (FXS), the most common genetic form of autism spectrum disorder, is caused by deficiency of the fragile X mental retardation protein (FMRP). Despite extensive research and scientific progress, understanding how FMRP regulates brain development and function remains a major challenge. FMRP is a neuronal RNA-binding protein that binds about a third of messenger RNAs in the brain and controls their translation, stability, and cellular localization. The absence of FMRP results in increased protein synthesis, leading to enhanced signaling in a number of intracellular pathways, including the mTOR, mGLuR5, ERK, Gsk3β, PI3K, and insulin pathways. Until recently, FXS was largely considered a deficit of mature neurons; however, a number of new studies have shown that FMRP may also play important roles in stem cells, among them neural stem cells, germline stem cells, and pluripotent stem cells. In this review, we will cover these newly discovered functions of FMRP, as well as the other two fragile X-related proteins, in stem cells. We will also discuss the literature on the use of stem cells, particularly neural stem cells and induced pluripotent stem cells, as model systems for studying the functions of FMRP in neuronal development.

Keywords: Adult stem cells; Developmental biology; FMRP; Fragile X syndrome; Nervous system; Neural differentiation; Neural stem cell; Pluripotent stem cells; Stem cell plasticity.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Embryonic Stem Cells / physiology
  • Fragile X Mental Retardation Protein / chemistry
  • Fragile X Mental Retardation Protein / physiology*
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism
  • Fragile X Syndrome / pathology*
  • Gene Expression Regulation
  • Humans
  • Mutation
  • Neural Stem Cells / physiology*
  • RNA-Binding Proteins / physiology


  • FMR1 protein, human
  • FXR1 protein, human
  • FXR2 protein, human
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein