Transcriptional profiling of sequentially generated septal neuron fates

eLife

Miguel Turrero García¹  Corey C Harwell¹  Sarah K Stegmann¹  Manal A Adam¹  Sinisa Hrvatin¹  Tiara E Lacey²  Christopher M Reid³  M Aurel Nagy³  Caleb Weinreb⁴ 

[1] Department of Neurobiology, Harvard Medical School, Boston, United States;Department of Neurobiology, Harvard Medical School, Boston, United States;Biological and Biomedical Sciences PhD program at Harvard University, Cambridge, United States;Department of Neurobiology, Harvard Medical School, Boston, United States;PhD Program in Neuroscience at Harvard University, Cambridge, United States;Department of Systems Biology, Harvard Medical School, Boston, United States;PhD Program in Systems Biology at Harvard University, Cambridge, United States;

关键词: septal nucleus;    neurogenesis;    cell fate;    transcription factors;    Mouse;   

DOI  :  10.7554/eLife.71545

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY