期刊
ELIFE
卷 10, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.71545
关键词
septal nucleus; neurogenesis; cell fate; transcription factors; Mouse
类别
资金
- National Institute of Mental Health [R01MH119156]
- National Institute of Neurological Disorders and Stroke [R01NS102228]
- Ellen and Melvin Gordon Center for the Cure of Paralysis Fellowship
- Boehringer Ingelheim Fonds MD Fellowship
- Bill and Melinda Gates Foundation
- Howard Hughes Medical Institute Gilliam Fellowship for Advanced Study
- Harvard Brain Science Initiative
- Giovanni ArmeniseHarvard Foundation
This study investigates how septal neuron diversity is established during neurogenesis, revealing that septal eminence progenitors differ from rostral septal progenitors in molecular profiles, proliferative capacity, and fate potential. Specifically, Nkx2.1-expressing septal eminence progenitors give rise to neurons of at least three morphological classes, born in temporal cohorts distributed across different septal nuclei in a sequential pattern.
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.
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