DrosophilaActivin-β and the Activin-like product Dawdle function redundantly to regulate proliferation in the larval brain

Abstract

The Drosophila Activin-like ligands Activin-β and Dawdle control several aspects of neuronal morphogenesis, including mushroom body remodeling, dorsal neuron morphogenesis and motoneuron axon guidance. Here we show that the same two ligands act redundantly through the Activin receptor Babo and its transcriptional mediator Smad2 (Smox), to regulate neuroblast numbers and proliferation rates in the developing larval brain. Blocking this pathway results in the development of larvae with small brains and aberrant photoreceptor axon targeting, and restoring babo function in neuroblasts rescued these mutant phenotypes. These results suggest that the Activin signaling pathway is required for producing the proper number of neurons to enable normal connection of incoming photoreceptor axons to their targets. Furthermore, as the Activin pathway plays a key role in regulating propagation of mouse and human embryonic stem cells, our observation that it also regulates neuroblast numbers and proliferation in Drosophilasuggests that involvement of Activins in controlling stem cell propagation may be a common regulatory feature of this family of TGF-β-type ligands.

Neuroendocrine regulation of Drosophila metamorphosis requires TGFβ/Activin signaling

“…The strains used include daw-Gal4 (Zhu et al, 2008), Act-Gal4 (Ting et al, 2007), UAS-babo(CA) (Brummel et al, 1999), phm-Gal4 (Ono et al, 2006) and UAS-Rheb EP50.084 (Chang and Neufeld, 2009). UAS-dSmad2 RNAi (#14609 and #105687), UAS-babo RNAi (#3825 and #853), UAS-punt RNAi (#848 and #37279) and UASmedea RNAi (#19688 and #19689) were obtained from the Vienna Drosophila RNAi center.…”

Drosophila asymmetric division, polarity and cancer

“…Indeed, NBs occupy defined anatomical positions during development and are in close contact with neighbouring cells: their most recent daughters on the basal side (Truman and Bate, 1988), and cortex glial cells on their apical and lateral sides (Dumstrei et al, 2003). Moreover, NBs are not insensitive to their neighbours and are definitively responsive to signals like Anachronism or Activin, which are secreted by larval glia (Ebens et al, 1993;Zhu et al, 2008) as well as to Notch, and other signalling pathways that control the number of proliferating NBs in the larval brain (Park et al, 2003;Wang et al, 2006;Lee et al, 2006a). However, the presence of a cell niche necessary for maintaining the NB self-renewing asymmetric division programme has not been demonstrated (Doe, 2008).…”

Activin signaling balances proliferation and differentiation of ovarian niche precursors and enables adjustment of niche numbers

“…Babo phosphorylates the R-Smad Smox (Smad on X), which, together with the Smad4 homolog Medea, translocates to the nucleus and represses or activates various target genes (Brummel et al, 1999). Activin has been associated with proliferation, differentiation and morphogenetic events occurring in the nervous system, immune system, muscle and during imaginal disc development (Bai et al, 2013;Brummel et al, 1999;Clark et al, 2011;Ellis et al, 2010;Ng, 2008;Parker et al, 2006;Peterson and O'Connor, 2013;Ting et al, 2014;Yu et al, 2013;Zheng et al, 2003;Zhu et al, 2008). Activin signaling also acts systemically to control metamorphosis by promoting the expression of several ecdysone biosynthetic enzymes (Gibbens et al, 2011).…”