TGFb/Activin signalling is required for ribosome biogenesis and cell growth in Drosophila salivary glands

Signalling by TGFβ superfamily factors plays an important role in tissue growth and cell proliferation. In Drosophila, the activity of the TGFβ/Activin signalling branch has been linked to the regulation of cell growth and proliferation, but the cellular and molecular basis for these functions are not fully understood. In this study, we show that both the RII receptor Punt (Put) and the R-Smad Smad2 are strongly required for cell and tissue growth. Knocking down the expression of Put or Smad2 in salivary glands causes alterations in nucleolar structure and functions. Cells with decreased TGFβ/Activin signalling accumulate intermediate pre-rRNA transcripts containing internal transcribed spacer 1 regions accompanied by the nucleolar retention of ribosomal proteins. Thus, our results show that TGFβ/Activin signalling is required for ribosomal biogenesis, a key aspect of cellular growth control. Importantly, overexpression of Put enhanced cell growth induced by Drosophila Myc, a well-characterized inducer of nucleolar hypertrophy and ribosome biogenesis.This work was supported by project Norte-01-0145-FEDER000029, Advancing Cancer Research: From Basic Knowledge to Application, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by National Funds through FCT–‘Fundaçâo para a Ciência e a Tecnologia’ under the project FCOMP-01-0124-FEDER015675 (PTDC/SAU-BID/112250/2009). T.M. was supported by an FCT Fellowship ALTF 677-2012, and N.E. was supported by a PhD FCT Fellowship SFRH/BD/95087/2013. P.S.P. is a recipient of a Portuguese ‘Investigator FCT’ contract.Peer reviewe