A FGF-Hh feedback loop controls stem cell proliferation in the developing larval brain of drosophila melanogaster

Abstract

The adult Drosophila central nervous system is produced by two phases of neurogenesis: the first phase occurs during embryonic development where the larval brain is formed and the second occurs during larval development to form the adult brain. Neurogenesis in both phases is caused by the activation of neural stem cell division and subsequent progenitor cell division and terminal differentiation. Proper activation of neural stem cell division in the larval brain is essential for proper patterning and functionality of the adult central nervous system. Initiation of neural stem cell proliferation requires signaling from the Fibroblast Growth Factor (FGF) homolog Branchless (Bnl) and by the Hedgehog (Hh) growth factor. I have focused on the interactions between both of these signaling pathways with respect to post-embryonic neural stem cell proliferation using the Drosophila larval brain. Using proliferation assays and quantitative real-time PCR, I have shown that Bnl and Hh signaling is inter-dependent in the 1st instar larval brain and activates neural stem cell proliferation. I have also shown that overexpression of bnl can rescue signaling and neuroblast proliferation in a hh mutant. However, overexpression of hh does not rescue signaling or neuroblast proliferation in a bnl mutant, suggesting that Bnl is the signaling output of the Bnl-Hh feedback loop and that all central brain and optic lobe neural stem cells require Bnl signaling to initiated proliferation.