PT  - JOURNAL ARTICLE
AU  - Yiyun Zhou
AU  - Sarah E. Popadowski
AU  - Emily Deustchman
AU  - Marc S. Halfon
TI  - Distinct roles and requirements for <em>Ras</em> pathway signaling in visceral versus somatic muscle founder specification
AID  - 10.1101/347526
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 347526
4099  - http://biorxiv.org/content/early/2018/06/14/347526.short
4100  - http://biorxiv.org/content/early/2018/06/14/347526.full
AB  - Pleiotropic signaling pathways must somehow engender specific cellular responses. In the Drosophila mesoderm, Ras pathway signaling specifies muscle founder cells from among the broader population of myoblasts. For somatic muscles, this is an inductive process mediated by the ETS-domain downstream Ras effectors Pointed and Aop (Yan). We demonstrate here that for the circular visceral muscles, despite superficial similarities, a significantly different specification mechanism is at work. Not only is visceral founder cell specification not dependent on Pointed or Aop, but Ras pathway signaling in its entirety can be bypassed. Our results show that de-repression, not activation, is the predominant role of Ras signaling in the visceral mesoderm and that accordingly, Ras signaling is not required in the absence of repression. The key repressor acts downstream of the transcription factor Lameduck and is likely a member of the ETS transcription factor family. Our findings fit with a growing body of data that point to a complex interplay between the Ras pathway, ETS transcription factors, and enhancer binding as a critical mechanism for determining unique responses to Ras signaling.SUMMARY A fundamentally different mechanism is shown for how Ras signaling governs cell fate specification in the Drosophila somatic versus visceral mesoderms, providing insight into how signaling specificity is achieved.