Affiliation:
1. Department of Neurobiology, Harvard Medical School
2. Biological and Biomedical Sciences PhD program at Harvard University
3. PhD Program in Neuroscience at Harvard University
4. Department of Systems Biology, Harvard Medical School
5. PhD Program in Systems Biology at Harvard University
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.
Funder
National Institute of Mental Health
National Institute of Neurological Disorders and Stroke
Ellen and Melvin Gordon Center for the Cure of Paralysis
Boehringer Ingelheim Fonds
Bill and Melinda Gates Foundation
Howard Hughes Medical Institute
Harvard Brain Science Initiative
Giovanni Armenise-Harvard Foundation
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Cited by
9 articles.
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