Abstract
Despite the crucial physiological processes governed by neurons in the hypothalamic arcuate nucleus (ARC), such as growth, reproduction and energy homeostasis, the developmental pathways and regulators for ARC neurons remain understudied. Our single cell RNA-seq analyses of mouse embryonic ARC revealed many cell type-specific markers for developing ARC neurons. These markers include transcription factors whose expression is enriched in specific neuronal types and often depleted in other closely-related neuronal types, raising the possibility that these transcription factors play important roles in the fate commitment or differentiation of specific ARC neuronal types. We validated this idea with the two transcription factors, Foxp2 enriched for Ghrh-neurons and Sox14 enriched for Kisspeptin-neurons, using Foxp2- and Sox14-deficient mouse models. Taken together, our single cell transcriptome analyses for the developing ARC uncovered a panel of transcription factors that are likely to form a gene regulatory network to orchestrate fate specification and differentiation of ARC neurons.
Original language | English |
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Article number | 3696 |
Pages (from-to) | 1-12 |
Journal | Nature Communications |
Volume | 10 |
Issue number | 1 |
Early online date | 16 Aug 2019 |
DOIs | |
Publication status | Published - 16 Aug 2019 |
Keywords
- Animals
- Arcuate Nucleus of Hypothalamus/cytology
- Forkhead Transcription Factors/genetics
- Gene Expression Profiling
- Gene Expression Regulation, Developmental
- Growth Hormone-Releasing Hormone/metabolism
- Kisspeptins/metabolism
- Mice
- Mice, Knockout
- Neurogenesis/genetics
- Neurons/metabolism
- Repressor Proteins/genetics
- SOXB2 Transcription Factors/genetics
- Single-Cell Analysis