Mammary Stem Cell Self-Renewal Is Regulated by Slit2/Robo1 Signaling through SNAI1 and mINSC.

ABSTRACT: Tissue homeostasis requires somatic stem cell maintenance; however, mechanisms regulating this process during organogenesis are not well understood. Here, we identify asymmetrically renewing basal and luminal stem cells in the mammary end bud. We demonstrate that SLIT2/ROBO1 signaling regulates the choice between self-renewing asymmetric cell divisions (ACDs) and expansive symmetric cell divisions (SCDs) by governing Inscuteable (mInsc), a key member of the spindle orientation machinery, through the transcription factor Snail (SNAI1). Loss of SLIT2/ROBO1 signaling increases SNAI1 in the nucleus. Overexpression of SNAI1 increases mInsc expression, an effect that is inhibited by SLIT2 treatment. Increased mInsc does not change cell proliferation in the mammary gland (MG) but instead causes m

SUBMITTER: Ballard MS 

PROVIDER: S-EPMC4606466 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature