PgmNr D1214: Hrb27C functionally interacts with ecdysone signaling to maintain the Drosophila female germline stem cell fate.

Authors:
Danielle S. Finger; Elizabeth T. Ables


Institutes
East Carolina University, Greenville, NC.


Keyword: germline stem cell

Abstract:

Stem cells maintain an undifferentiated fate while creating new daughters destined for differentiation.  Effective use of stem cells as tools for clinical therapy requires a detailed understanding of the molecular mechanisms that control their fate in vivo. A variety of molecular signals influence stem cell fate, including local signals from adjacent cells and long-range hormonal signals; however, little is known about how hormones promote the undifferentiated fate. Germline stem cells (GSCs) in the Drosophila melanogaster ovary are an ideal model to study the mechanisms of stem cell maintenance on a per-cell basis in vivo. GSCs are known to be directly regulated by the steroid hormone ecdysone, which is structurally and functionally similar to human sex hormones.  Using a forward genetic screen, we identified Heterogeneous nuclear ribonucleoprotein at 27C (Hrb27C) as a potential downstream target of ecdysone signaling. Hrb27C is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family of RNA binding proteins that aid in the localization, maturation, and translation of newly formed RNAs. To investigate whether and how Hrb27C regulates GSC maintenance we used Flippase/Flippase Recognition Target (FLP/FRT)-mediated recombination to create homozygous Hrb27C mutant GSCs, and used molecular markers to track their fate. Our results demonstrated that Hrb27C mutants display greater GSC loss than their respective controls, indicating that Hrb27C is required for GSC maintenance. This loss is due to deregulation of pMAD, a component of the BMP signaling pathway that is required for repressing differentiation of GSCs.  Further, non-allelic non-complementation experiments demonstrated that Hrb27C functionally interacts with both ecdysone signaling and BMP signaling to control GSC number. Taken together, these results suggest a model wherein Hrb27C mediates the effects of ecdysone signaling in GSCs. Future experiments will be aimed at determining if other hnRNPs work independently or in complex with Hrb27C to control GSC maintenance. This will increase our understanding of the function of Hrb27C and the hnRNP family in the regulation of stem cell fate, and provide insight into the mechanisms by which steroid hormones maintain stem cell fate in adults in vivo.