Germline stem cells and their regulation in the nematode Caenorhabditis elegans

Adv Exp Med Biol. 2013;786:29-46. doi: 10.1007/978-94-007-6621-1_3.

Abstract

C. elegans germline stem cells exist within a stem cell pool that is maintained by a single-celled mesenchymal niche and Notch signaling. Downstream of Notch signaling, a regulatory network governs stem cells and differentiation. Central to that network is the FBF RNA-binding protein, a member of the widely conserved PUF family that functions by either of two broadly conserved mechanisms to repress its target mRNAs. Without FBF, germline stem cells do not proliferate and they do not maintain their naïve, undifferentiated state. Therefore, FBF is a pivotal regulator of germline self-renewal. Validated FBF targets include several key differentiation regulators as well as a major cell cycle regulator. A genomic analysis identifies many other developmental and cell cycle regulators as likely FBF targets and suggests that FBF is a broad-spectrum regulator of the genome with >1,000 targets. A comparison of the FBF target list with similar lists for human PUF proteins, PUM1 and PUM2, reveals ∼200 shared targets. The FBF hub works within a network controlling self-renewal vs. differentiation. This network consists of classical developmental cell fate regulators and classical cell cycle regulators. Recent results have begun to integrate developmental and cell cycle regulation within the network. The molecular dynamics of the network remain a challenge for the future, but models are proposed. We suggest that molecular controls of C. elegans germline stem cells provide an important model for controls of stem cells more broadly.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Cycle / genetics
  • Cell Differentiation
  • Cell Proliferation
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks
  • Germ Cells / cytology
  • Germ Cells / metabolism*
  • Humans
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Signal Transduction
  • Stem Cell Niche / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptors, Notch
  • fem-3-binding protein, C elegans