Extrinsic Activin signaling cooperates with an intrinsic temporal program to increase mushroom body neuronal diversity

Abstract

Temporal patterning of neural progenitors leads to the sequential production of diverse neuronal types. To better understand how extrinsic cues interact with intrinsic temporal programs to contribute to temporal patterning, we studied the Drosophila mushroom body neural progenitors (neuroblasts). Each of these four neuroblasts divides ~250 times to sequentially produce only three main neuronal types over the course of ~9 days of development: {gamma}, followed by {beta}, and finally {beta} neurons. The intrinsic temporal clock is composed of two RNA-binding proteins, IGF-II mRNA binding protein (Imp) and Syncrip (Syp), that are expressed in opposing temporal gradients. Activin signaling affects the production of {beta} neurons but whether and how this extrinsic cue interacts with the intrinsic temporal program was not known. We show that the Activin ligand Myoglianin produced from glia regulates the levels of the intrinsic temporal factor Imp in mushroom body neuroblasts. In neuroblasts mutant for the Activin signaling receptor baboon, Imp levels are higher than normal during the {beta} temporal window, leading to the specific loss of the {beta} neurons. The intrinsic temporal clock still progresses but with a delay, skipping the {beta} window without affecting the total number of neurons produced: The number of {gamma} neurons increases, {beta} disappear and the number of {beta} neurons decreases. Our results illustrate that an extrinsic cue modifies an intrinsic temporal program to increase neuronal diversity.