Combinatorial use of translational co-factors for cell type-specific regulation during neuronal morphogenesis in Drosophila

Abstract

The translational regulators Nanos (Nos) and Pumilio (Pum) work together to regulate the morphogenesis of dendritic arborization (da) neurons of the Drosophila larval peripheral nervous system. In contrast, Nos and Pum function in opposition to one another in the neuromuscular junction to regulate the morphogenesis and the electrophysiological properties of synaptic boutons. Neither the cellular functions of Nos and Pum nor their regulatory targets in neuronal morphogenesis are known. Here we show that Nos and Pum are required to maintain the dendritic complexity of da neurons during larval growth by promoting the outgrowth of new dendritic branches and the stabilization of existing dendritic branches, in part by regulating the expression of cut and head involution defective. Through an RNA interference screen we uncover a role for the translational co-factor Brain Tumor (Brat) in dendrite morphogenesis of da neurons and demonstrate that Nos, Pum, and Brat interact genetically to regulate dendrite morphogenesis. In the neuromuscular junction, Brat function is most likely specific for Pum in the presynaptic regulation of bouton morphogenesis. Our results reveal how the combinatorial use of co-regulators like Nos, Pum and Brat can diversify their roles in post-transcriptional regulation of gene expression for neuronal morphogenesis.

Nanos-mediated repression of hid protects larval sensory neurons after a switch in sensitivity to apoptotic signals

“…The conserved RNA-binding proteins Nanos (Nos) and Pumilio (Pum) function together to regulate dendrite morphogenesis in Drosophila (Brechbiel and Gavis, 2008;Olesnicky et al, 2012;Ye et al, 2004). Class IV da neurons in both nos and pum mutant larvae exhibit a dramatic decrease in dendritic arbor complexity, characterized by a reduction of higher order branches, as well as a field coverage defect (Brechbiel and Gavis, 2008;Olesnicky et al, 2012;Ye et al, 2004).…”

“…Class IV da neurons in both nos and pum mutant larvae exhibit a dramatic decrease in dendritic arbor complexity, characterized by a reduction of higher order branches, as well as a field coverage defect (Brechbiel and Gavis, 2008;Olesnicky et al, 2012;Ye et al, 2004). In the early embryo, Nos and Pum form a localized translational repressor complex essential for abdominal and germline development (Vardy and Orr-Weaver, 2007).…”

“…Similarly, nos function in class IV da neurons requires dendritic localization of nos mRNA, suggesting that Nos and Pum act locally within dendrites to regulate target mRNAs important for dendrite morphogenesis (Brechbiel and Gavis, 2008). Because the dendritic arborization defects in nos and pum mutants arise after the initial elaboration of the dendritic arbors, Nos and Pum are thought to function in maintaining dendritic field complexity during late larval development (Brechbiel and Gavis, 2008;Olesnicky et al, 2012). Why Nos and Pum are required particularly during late larval development and their specific regulatory role in maintenance remains unknown.…”

“…We previously found that levels of the pro-apoptotic factor Hid are elevated in class IV da neurons mutant for nos or pum (Olesnicky et al, 2012). Nos and its orthologs play essential roles in preventing apoptosis of primordial germ cells (PGCs), which in Drosophila requires Nos-mediated repression of hid (Lai and King, 2013;Sato et al, 2007).…”

A Drosophila melanogaster ivarvonal-fejlődésében szerepet játszó gének azonosítása és vizsgálata

“…Kimutatták, hogy kifejlett állatokban a Mei-P26 transzlációs korepresszorként fizikai kölcsönhatást képes kialakítani a Nos fehérjével a csíravonal őssejtekben [128]. Más sejttípusokban azt találták, hogy a Nos fehérjekomplexet képez a Mei-P26-hoz hasonló TRIM-NHL fehérjével, a Brain tumor-ral (Brat), mellyel célgének mRNS-e -például a CycB mRNS-e -transzlációs represszoraként képesek viselkedni [186][187][188]. Embrionális ivarsejtekben a Brat nem szükséges a CycB Nos-függő transzlációs repressziójához [188].…”