Molecular “noise” aids cell differentiation

Researchers have used the common fruit fly, Drosophila melanogaster, as a model organism in genetics studies for decades due to their small size, short gestation period, and completely sequenced genome. (Source: Wikipedia Commons, Credit: Martin Cooper)

The ability of a cell to differentiate, or become more specialized in structure and function, entails a complex series of molecular interactions. Transcription factors represent one class of molecules that help control this process by turning specific genes on or off (1). However, if transcription factors mutate and cannot regulate differentiation, the cell may become cancerous. A team of researchers at Northwestern University studying how transcription factors behave stumbled across a new step in the cell differentiation process, providing new methods to identify how cancer develops (2).

The team observed the expression of the transcription factors Yan and Pnt, which help regulate the development of compound eyes in fruit flies (1). The activity of Yan and Pnt within a cell is determined by the presence of a third molecule, known as epidermal growth factor receptor (EGFR) (1). While previous models suggest that the presence of EGFR causes concentrations of Yan and Pnt to remain inversely proportional to each other, the amount of Yan and Pnt in fruit fly eye cells seem to fluctuate in direct proportion (1).

Using new yellow fluorescent proteins and image analysis software, researchers were able to track Yan activity within individual fruit fly cells as they developed from unspecialized embryonic cells to mature eye cells. Because Yan was thought to drive cell differentiation, the team was surprised to find that the cell matured independently of Yan concentrations (1). Instead, as the cell transitioned into maturity, data showed that Yan concentrations oscillated briefly, a phenomenon termed “Yan noise” (1).

Co-author Dr. Richard Carthew explained, this “noise is a state of ‘in between’ and is important for cells to switch to a more specialized state. This limbo might be where normal cells take a cancerous path” (2). The regulatory molecule EGFR was shown to play a key role in diminishing the noise and promoting cell differentiation (1). Further research into the regulation of noise in cancer cells may provide insight toward the development of new treatments.

Works Cited:

1. Peláez, N., Gavalda-Miralles, A., Wang, B., Navarro, H. T., Gudjonson, H., Rebay, I., … & Carthew, R. W. (2016). Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation. eLife, 4, e08924. doi: 10.7554/eLife.08924
2. Northwestern University. (2016, January 20). Researchers pinpoint place where cancer cells may begin: Scientists use fruit fly genetics to understand how things could go wrong in cancer. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2016/01/160120201336.htm

Contact brenda.y.miao.19@dartmouth.edu with questions.