Essential role of grim-led programmed cell death for the establishment of corazonin-producing peptidergic nervous system during embryogenesis and metamorphosis in Drosophila melanogaster

Abstract

SummaryIn Drosophila melanogaster, combinatorial activities of four death genes, head involution defective (hid), reaper (rpr), grim, and sickle (skl), have been known to play crucial roles in the developmentally regulated programmed cell death (PCD) of various tissues. However, different expression patterns of the death genes also suggest distinct functions played by each. During early metamorphosis, a great number of larval neurons unfit for adult life style are removed by PCD. Among them are eight pairs of corazonin-expressing larval peptidergic neurons in the ventral nerve cord (vCrz). To reveal death genes responsible for the PCD of vCrz neurons, we examined extant and recently available mutations as well as RNA interference that disrupt functions of single or multiple death genes. We found grim as a chief proapoptotic gene and skl and rpr as minor ones. The function of grim is also required for PCD of the mitotic sibling cells of the vCrz neuronal precursors (EW3-sib) during embryonic neurogenesis. An intergenic region between grim and rpr, which, it has been suggested, may enhance expression of three death genes in embryonic neuroblasts, appears to play a role for the vCrz PCD, but not for the EW3-sib cell death. The death of vCrz neurons and EW3-sib is triggered by ecdysone and the Notch signaling pathway, respectively, suggesting distinct regulatory mechanisms of grim expression in a cell- and developmental stage-specific manner.

Cloning and functional characterizations of an apoptogenic Hid gene in the Scuttle Fly, Megaselia scalaris (Diptera; Phoridae)

“…For instance, metamorphosis-associated degeneration of the salivary glands requires reaper and Hid (Jiang et al, 2000), while Hid is necessary for cell death in response to the depletion of the survival signal (Kuroda and White, 1998; Bergmann et al, 2002). On the other hand, we and others have shown that grim is the principal death inducer for developmentally-regulated PCD of larval neurons producing Corazonin, bursicon, and CCAP neuropeptides (Draizen et al, 1999; Lee et al, 2013a, 2013b). …”

Notch signaling and neuronal death in stroke

“…In the developing nerve cord of Drosophila , active Notch signaling dictates death of the dying lineages, while inactive Notch promotes death of hemilineages (Lundell et al, 2003; Lee et al, 2013). Notch has also been reported to induce apoptosis in other Drosophila tissues (Orgogozo et al, 2002; Yu et al, 2002).…”

Programmed cell death acts at different stages of Drosophila neurodevelopment to shape the central nervous system

“…One lineage that has been studied extensively for its very stereotyped apoptosis is that of the ventral nerve chord neuroblast 7-3 (Lundell, Lee et al 2003, Karcavich and Doe 2005, Rogulja-Ortmann, Renner et al 2008, Lee, Sehgal et al 2013). In this lineage, the first GMC gives rise to the EW1 serotonergic interneuron and the GW motoneuron; the second GMC generates the EW2 serotonergic interneuron and a neuron that undergoes PCD; the third GMC generates the EW3 corazonin-positive (vCrz) interneuron and its apoptotic sibling.…”

“…All these binary cell fate or survival decisions are mediated by the asymmetric inheritance of Numb in one of the neuronal progeny, which inhibits Notch signaling in this cell. If the sibling of EW3 that undergoes PCD is forced to survive, it also differentiates as a vCrz interneuron (Novotny, Eiselt et al 2002, Lundell, Lee et al 2003, Karcavich and Doe 2005, Lee, Sehgal et al 2013). …”

“…reaper and grim are needed to trigger apoptosis of neuroblasts in the abdominal neuromeres (Tan, Yamada-Mabuchi et al 2011). grim appears to regulate apoptosis of neuropeptide-expressing neurons, such as the vCrz (in collaboration with reaper ) (Choi, Lee et al 2006, Lee, Sehgal et al 2013), Capability-expressing Va neurons (Suska, Miguel-Aliaga et al 2011), and CCAP-expressing neurons (Lee, Kikuno et al 2013). It is also important to highlight that even if one of the RHG genes is not expressed in an apoptotic cell, it is often sufficient to trigger apoptosis if mis-expressed in this cell; e.g .…”