Transcriptional profiling of sequentially generated septal neuron fates
- Harvard Medical School, United States
Abstract
The septum is a ventral forebrain structure known to regulate innate behaviors. During embryonic development, septal neurons are produced in multiple proliferative areas from neural progenitors following transcriptional programs that are still largely unknown. Here, we use a combination of single cell RNA sequencing, histology and genetic models to address how septal neuron diversity is established during neurogenesis. We find that the transcriptional profiles of septal progenitors change along neurogenesis, coinciding with the generation of distinct neuron types. We characterize the septal eminence, an anatomically distinct and transient proliferative zone composed of progenitors with distinctive molecular profiles, proliferative capacity and fate potential compared to the rostral septal progenitor zone. We show that Nkx2.1-expressing septal eminence progenitors give rise to neurons belonging to at least three morphological classes, born in temporal cohorts that are distributed across different septal nuclei in a sequential fountain-like pattern. Our study provides insight into the molecular programs that control the sequential production of different neuronal types in the septum, a structure with important roles in regulating mood and motivation.
Data availability
Sequencing data have been deposited in GEO under accession code GSE184879
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Data from: Transcriptional profiling of sequentially generated septal neuron fatesNCBI Gene Expression Omnibus, GSE184879.
Article and author information
Author details
Miguel Turrero García
Funding
National Institute of Mental Health (R01MH119156)
- Corey C Harwell
National Institute of Neurological Disorders and Stroke (R01NS102228)
- Corey C Harwell
Ellen and Melvin Gordon Center for the Cure of Paralysis (Fellowship)
- Miguel Turrero García
Boehringer Ingelheim Fonds (MD Fellowship)
- Sarah K Stegmann
Bill and Melinda Gates Foundation (Millennium Scholarship)
- Tiara E Lacey
Howard Hughes Medical Institute (Gilliam Fellowship for Advanced Study)
- Christopher M Reid
Harvard Brain Science Initiative (Seed Grant)
- Corey C Harwell
Giovanni Armenise-Harvard Foundation (Junior Faculty Award)
- Corey C Harwell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joseph G Gleeson, Howard Hughes Medical Institute, The Rockefeller University, United States
Ethics
Animal experimentation: All animal procedures conducted in this study followed experimental protocols approved by the Institutional Animal Care and Use Committee of Harvard Medical School (IS961-3 and IS677-3).
Version history
- Received: June 22, 2021
- Preprint posted: July 1, 2021 (view preprint)
- Accepted: November 22, 2021
- Accepted Manuscript published: December 1, 2021 (version 1)
- Version of Record published: December 22, 2021 (version 2)
Copyright
© 2021, Turrero García 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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Transcriptional profiling of sequentially generated septal neuron fates
eLife 10:e71545.
https://doi.org/10.7554/eLife.71545
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