Seven up acts as a temporal factor during two different stages of neuroblast 5-6 development

Abstract

Neural progenitor cells, in both vertebrates and invertebrates, go through temporal competence changes, evidenced by the generation of different classes of neurons and glia at different time points (Okano and Temple, 2009). These programmed changes are likely to be controlled by a combination of both extrinsic and intrinsic cues, and evidence points to the existence of both mechanisms in vertebrates and invertebrates. With respect to intrinsic cues, major progress has been made in the Drosophila melanogaster system, in particular in the embryonic ventral nerve cord (VNC). Here, temporal competence changes have been shown to be under control of an intrinsic temporal cascade of transcription factors, the temporal gene cascade (Brody and Odenwald, 2002;Jacob et al., 2008;Pearson and Doe, 2004). This cascade consist of the sequential expression, and function, of the Hunchback (Hb), Kruppel (Kr), Nubbin and Pdm2 (denoted collectively Pdm herein), Castor (Cas) and Grainy head (Grh) transcription factors, in a HbrKrrPdmrCasrGrh cascade. The precise progression of this cascade is an effect of mutually activating and repressing actions of the factors upon each other. In addition, studies have also identified factors that facilitate this progression, i.e. 'switching factors'. Here, the seven up (svp) and distal antenna/distal antenna related (collectively referred to as dan herein) genes have been shown to play important roles in ensuring the switch from HbrKr, by suppressing Hb (Kanai et al., 2005;Kohwi et al., 2011;Mettler et al., 2006). Both Svp and Dan display a second wave of expression, but their function here is unknown. Finally, our previous studies have also identified the existence of so-called 'sub-temporal' genes, which act downstream of the temporal genes, do not regulate temporal genes, and act to sub-divide larger temporal windows (Baumgardt et al., 2009). However, in spite of the progress in understanding temporal competence changes, it is not clear how neuroblasts switch from one competence window to the next, how window size is controlled and how windows are subdivided. Moreover, recent mathematical modelling of the temporal cascades, indicate the existence of additional players involved in the temporal competence changes observed in vivo (Nakajima et al., 2010).To address these issues, we are using the Drosophila embryonic thoracic neuroblast 5-6 (NB5-6T) as a model. This neuroblast, which can be readily identified by the specific expression of reporter genes under the control of an enhancer fragment from the ladybird early gene [lbe(K)] (De Graeve et al., 2004), is generated in each of the six thoracic VNC hemisegments. Each NB5-6T produces a mixed lineage of 20 cells, and the four last cells to be born are a set of four interneurons expressing the Apterous (Ap) LIM-homeodomain transcription factor: the Ap neurons (Baumgardt et al., 2009). The four Ap neurons can be further subdivided into three different neuronal sub-types: the Ap1/Nplp1 and Ap4/FMRFa neurons, expressing the Nplp1 and FMRFamide neurop...

Nuclear receptor signal transduction in C. elegans

“…Transcriptional profiling of unc-55 reveals differential expression in a large number of genes compared to wild type, including the Iroquois homeodomain protein IRX-1, which also regulates DD remodeling (Petersen et al, 2011). The UNC-55/HBL-1 regulatory interaction strikingly resembles those seen in Drosophila where seven-up/COUP temporally regulates hb/hunchback during neurogenesis (Kanai et al, 2005;Benito-Sipos et al, 2011).…”

Novel Genes Involved in Controlling Specification of Drosophila FMRFamide Neuropeptide Cells

“…svp was previously identified as being critical for proper down-regulation of Hb in the temporal cascade; however, this function does not in itself explain the phenotypes discovered in this screen. The identification of svp in the screen prompted us to recently investigate its function in greater detail, which revealed dual expression (Table 1), and is fully discussed elsewhere (Benito-Sipos et al 2011).…”

Klumpfuss controls FMRFamide expression by enabling BMP signaling within the NB5-6 lineage

“…S2A,B,F-I,Q-S). grh and svp mutants displayed an increase in the number of Ap neurons (Baumgardt et al, 2009;Benito-Sipos et al, 2011) and, accordingly, there was an increase in Ap neurons expressing Klu at stage 16 (supplementary material Fig. S2D,K,Q-S).…”

“…well as the subtemporal genes squeeze [sqz; mammalian CIZ (Znf384)], nab (mammalian Nab1/2) and seven up (svp; mammalian Nr2f1/2) (Baumgardt et al, 2009;Benito-Sipos et al, 2011;Terriente Félix et al, 2007). We observed no alteration in the expression of these temporal and subtemporal factors (supplementary material Fig.…”