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: g, followed by α'β', and finally αβ 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 α'β' 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 downregulates 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 α'β' temporal window, leading to the specific loss of the α'β' neurons. The intrinsic temporal clock still progresses but with a delay, skipping the α'β' window without affecting the total number of neurons produced: The number of g neurons likely increases, α'β' disappear, and the number of αβ neurons decreases. Our results illustrate that an extrinsic cue modifies an intrinsic temporal program to increase neuronal diversity.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Opposite Imp/Syp temporal gradients govern birth time-dependent neuronal fatesNCBI Gene Expression Omnibus, GSE71103.
Article and author information
Author details
Funding
National Eye Institute (R01 EY017916)
- Claude Desplan
National Institute of Neurological Disorders and Stroke (R21 NS095288)
- Claude Desplan
National Institutes of Health (T32 HD007520)
- Anthony M Rossi
New York University (GSAS MacCracken Program)
- Anthony M Rossi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Chris Q Doe, Howard Hughes Medical Institute, University of Oregon, United States
Version history
- Received: May 14, 2020
- Accepted: July 3, 2020
- Accepted Manuscript published: July 6, 2020 (version 1)
- Version of Record published: July 16, 2020 (version 2)
Copyright
© 2020, Rossi & Desplan
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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