Modulators of Spitz Group/Der Signaling Differentially Affect Midline Glia Survival and Differentiation

Abstract

In Drosophila melanogaster, the genes of the spitz group and of the DER signaling pathway function together to communicate localized developmental signals to the cells of many tissues. The embryonic midline glia (MG), a mesectodermal lineage essential to proper morphogenesis of the axon tracts of the ventral nerve cord (VNC), depend on spitz group signaling for survival and differentiation. Loss of function of any of the spitz group genes or of DER results in a decrease in the number of MG and subsequent defects in the formation of the axon tracts. These defects include a medial collapse of the longitudinal axons and fusion of the posterior and anterior commissures. Ectopic expression of Rhomboid, a putative seven pass transmembrane protein which is a member of the spitz group, generates supernumerary glia. Directed expression of DER^AB87T, an activated form of the Drosophila EGF receptor, sSpi, a diffusible ligand, or Ras^v12, a constitutively activated variant of a monomeric G-protein, have the same effect on MG number. It is proposed that the spitz group/DER signaling pathway act to promote survival of MG precursor cells. In addition, expression of Draf and pntP1 are found to increase the number of surviving supernumerary MG, however these signaling molecules are determined to be less effective at promoting the survival of the MG, based on their decreased ability to generate supernumerary MG. Furthermore, a subset of the supernumerary MG created in embryos in which Draf has been misexpressed appear to be incompletely differentiated or insulated from normal programmed cell death (PCD) by expression of this transgene. The effect of multiple cytoplasmic signaling pathways, activated by spitz group/DER signaling, on MG survival and differentiation is examined and discussed. Ectopic expression of rhomboid generates supernumerary MG. This process is suppressed by mutation of genes of the spitz group or of DER. Evidence that Rho functions upstream of Spi, Star and DER is presented. The implications of these data and their relevance to previously published models which propose the molecular actions of the spitz group/DER pathway genes are discussed. Finally, the role of spitz group/DER signaling in the activation of downstream target genes is explored. Overexpression of these genes results in increased expression of pointed, argos, and rhomboid. A model for spitz group function in signal amplification is proposed.