Role of Eiger/TNF-alpha in coordinating tissue growth in Drosophila

SANCHEZ, JUAN A. ; DEKANTY, ANDRES

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SAIB

How growth of tissues and organs are coordinated during animaldevelopment to give rise to well-proportioned structures, areunsolved questions in biology and are important to understand theorigin of human pathologies. Our previous work revealed a novelrole of the tumor suppressor protein Dp53 in coordinating growthbetween adjacent cell populations within a developing tissue. Byreducing the growth rates of defined territories in the wing primordiumof Drosophila, we showed that the tissue responds as a wholeand adjacent cell populations decrease their growth and proliferationrates. Dp53 plays a crucial role in regulating non-autonomouslythe reduction of tissue size and cell cycle proliferation and in itsabsence, the organ loses its normal proportions. By combininggene expression analysis and in vivo loss-of-function experiments,we identified eiger, the Drosophila homologue of mammalian TNFalpha,as a putative signaling molecules downstream of Dp53.Interestingly, eiger is induced in the growth-depleted territory in ap53-dependent manner and is required to coordinate growth. Eigerappears to act through its receptor Grindelwald and the JNK signalingpathway. These new findings indicate that Eiger might actas a tissue local signal, emerging as an important player in growthcoordination between adjacent cell populations.