Mamo decodes hierarchical temporal gradients into terminal neuronal fate
Temporal patterning is a seminal method of expanding neuronal diversity. Here we unravel a mechanism decoding neural stem cell temporal gene expression and transforming it into discrete neuronal fates. This mechanism is characterized by hierarchical gene expression. First, Drosophila neuroblasts express opposing temporal gradients of RNA-binding proteins, Imp and Syp. These proteins promote or inhibit chinmo translation, yielding a descending neuronal gradient. Together, first and second-layer temporal factors define a temporal expression window of BTB-zinc finger nuclear protein, Mamo. The precise temporal induction of Mamo is achieved via both transcriptional and post-transcriptional regulation. Finally, Mamo is essential for the temporally defined, terminal identity of α'/β' mushroom body neurons and identity maintenance. We describe a straightforward paradigm of temporal fate specification where diverse neuronal fates are defined via integrating multiple layers of gene regulation. The neurodevelopmental roles of orthologous/related mammalian genes suggest a fundamental conservation of this mechanism in brain development.
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.
Article and author information
Howard Hughes Medical Institute
- Tzumin Lee
National Institute of Neurological Disorders and Stroke (NS083085)
- Robert H Singer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States
- Received: April 29, 2019
- Accepted: September 20, 2019
- Accepted Manuscript published: September 23, 2019 (version 1)
- Version of Record published: September 27, 2019 (version 2)
© 2019, Liu et al.
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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