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

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.DOI: http://dx.doi.org/10.7554/eLife.08924.001

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“…In Drosophila, the expression noise of the transcription factor Yan responsible for maintaining eye cells in a multipotent state is transiently increased as cells transited to differentiation . Signals received from the EGF receptor are necessary for the transience and for eye cells to differentiate so that eye differentiated cell states are stabilized through noise reduction of Yan .…”

“…63 Signals received from the EGF receptor are necessary for the transience and for eye cells to differentiate so that eye differentiated cell states are stabilized through noise reduction of Yan. 63 Thus the authors suggested that dynamic heterogeneity of Yan is a necessary element of the transition process, and that cellular communications are essential in stabilizing and homogenizing gene expression during cell differentiation. A similar mechanism was already described in C. elegans embryos where the absence of some Frizzled receptors activating the Wnt pathway increases mab-5 expression variability in Q neuroblasts.…”