Pipsqueak family genes dan/danr antagonize nuclear Pros and prevent premature decommission of neural stem cells in Drosophila third instar larval brains

Abstract: Background Neural stem cell fate is regulated for the systematic production of a precise quantity of neurons during the development of the central nervous system. Results Here we found that two Drosophila pipsqueak family genes, distal antenna (dan) and distal antenna-related (danr), promote the proliferation of neural stem cells, termed neuroblasts (NBs), in third instar larval brains. In the absence of Dan and Danr (Dan/Danr), the NBs produce fewer daughter cells with smaller MARCM clone (lineage) sizes. The larval brain NBs in dan/danr clones show premature accumulation of nuclear Prospero (Pros), which only appears in the wildtype (wt) terminating NBs at early pupal stage. The premature nuclear Pros leads to NBs cell cycle defects and NB marker loss. Removal of Pros from dan/danr MARCM clones prevents lineage size shrinkage and rescues the loss of NB marker expression. Our data show that the appearance of nuclear Pros is behind the downregulation of Dan/Danr in the wt terminating NBs. We demonstrate that Dan/Danr and nuclear Pros are mutually exclusive in NBs. In addition, Dan/Danr are partially required for the late temporal regulator, Grainyhead (Grh), in third instar larval brain NBs. Conclusion Together our study uncovers the novel function of Dan/Danr in NB cell fate maintenance. Dan/Danr antagonize nuclear Pros, preventing NBs from premature decommission in Drosophila third instar larval brains.