In the developing Drosophila eye, glial cells must proliferate, migrate across other glial cells onto the imaginal eye disc, and differentiate to wrap axons of photoreceptor neurons. Franzdóttir et al. noticed that the mRNA for the fibroblast growth factor (FGF) receptor heartless (htl) was expressed at the front of migrating glial cells. Reduction of htl function in glial cells by expression of a dominant-negative form or by RNA interference (RNAi) decreased glial cell numbers, migration, and differentiation. The mRNAs encoding the FGF receptor ligands Pyramus (Pyr) and Thisbe (Ths) were expressed by glial cells and photoreceptor neurons, respectively, leading the authors to reason that these ligands might account for the ability of htl to regulate diverse aspects of glial cell behavior during development. Proliferation and motility were decreased by loss of Pyr function in glial cells (elicited by a hypomorphic allele of Pyr or by RNAi directed against Pyr) and increased by overexpression of Pyr in glial cells or the eye disc. In contrast, differentiation (as assessed by axonal wrapping) was reduced by neuron-specific RNAi directed against Ths and increased by neuronal overexpression of Ths. FGF receptors activate Dof (Downstream of FGF receptor); as expected, glial cell–specific loss of function of Dof produced effects (reduced glial cell numbers and reduced numbers of wrapping glia) reminiscent of those seen with loss of Htl function. Dof stimulates small G proteins in the Ras-MAPK (mitogen-activated protein kinase) family, which then activate transcription factors. Pyr appeared to activate Rap1 through Dof, because glial cell–specific RNAi directed against Rap1 inhibited proliferation and migration but not differentiation. In contrast, Ths appeared to activate the MAPK Rolled and the transcription factor Pointed, because glial cell–specific RNAi directed against Rolled or Pointed blocked only differentiation. FGF signaling is inhibited by Sprouty, and sprouty expression was detected in glial cells that had reached photoreceptor neurons. RNAi directed against Sprouty caused excessive axonal wrapping, suggesting that Sprouty limits FGF signaling in differentiated glial cells. Thus, FGF receptors modulate two separate aspects of glial cell activity during the eye development through two different ligands that activate distinct downstream signaling pathways.
S. R. Franzdóttir, D. Engelen, Y. Yuva-Aydemir, I. Schmidt, A. Aho, C. Klämbt, Switch in FGF signalling initiates glial differentiation in the Drosophila eye. Nature 460, 758–761 (2009). [PubMed]