The putative tumor suppressor Madm (Mlf1-adaptor molecule) regulates stem cell competition in Drosophila adult testis

Wednesday, September 24, 2014 — Poster Session IV
10:00 a.m. –12:00 p.m.	FAES Academic Center	NCI	STEMCELL-5

* FARE Award Winner

Authors

• SR Singh
• Y Liu
• SX Hou

Abstract

Myeloid leukemia factor 1 (Mlf1) is an oncogene involved in acute myeloid leukemia. Madm is a novel Mlf1 adaptor protein that opposes Mlf1’s function in regulating M1 myeloid cells differentiation. However, the functional mechanism of Madm is largely unknown. In the Drosophila testis, both germline and somatic stem cells share a local microenvironment or niche. The JAK-STAT signaling is required for maintenance of the two types of stem cells. Here we show that Madm functions in somatic stem cells and regulate competition of germline and somatic stem cells for niche occupation. We found that Madm negatively regulates the STAT92E, integrin and p-dERK expression in somatic stem cells. The JAK-STAT signaling regulates Madm nuclear translocation. We further demonstrated that Madm regulates stem cell competition by negatively regulating EGFR pathway through repressing vein (vn-the ligand of EGFR) in somatic stem cells. In addition, we found that activated EGFR pathway up-regulates integrin expression and somatic stem cells out-competing germline stem cells. Further, we found that knockdown Madm in somatic stem cells has similar phenotypes as overexpression of Mlf1. Therefore, our study has identified that Madm controls stem cell competition and functions as a tumor suppressor in Drosophila through negatively regulating the EGFR pathway.

back to top