Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation

Elife. 2015 Nov 19:4:e08924. doi: 10.7554/eLife.08924.

Abstract

Yan is an ETS-domain transcription factor responsible for maintaining Drosophila eye cells in a multipotent state. Yan is at the core of a regulatory network that determines the time and place in which cells transit from multipotency to one of several differentiated lineages. Using a fluorescent reporter for Yan expression, we observed a biphasic distribution of Yan in multipotent cells, with a rapid inductive phase and slow decay phase. Transitions to various differentiated states occurred over the course of this dynamic process, suggesting that Yan expression level does not strongly determine cell potential. Consistent with this conclusion, perturbing Yan expression by varying gene dosage had no effect on cell fate transitions. However, we observed that as cells transited to differentiation, Yan expression became highly heterogeneous and this heterogeneity was transient. Signals received via the EGF Receptor were necessary for the transience in Yan noise since genetic loss caused sustained noise. Since these signals are essential for eye cells to differentiate, we suggest that dynamic heterogeneity of Yan is a necessary element of the transition process, and cell states are stabilized through noise reduction.

Keywords: D. melanogaster; EGF Receptor; computational biology; developmental biology; eye development; retinal cell differentiation; stem cells; systems biology.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation*
  • Drosophila / embryology*
  • Drosophila Proteins / metabolism*
  • Eye / embryology
  • Eye Proteins / metabolism*
  • Gene Expression Regulation*
  • Repressor Proteins / metabolism*

Substances

  • AOP protein, Drosophila
  • Drosophila Proteins
  • Eye Proteins
  • Repressor Proteins