Single cell RNA-Seq identifies mechanisms controlling hypothalamic patterning and differentiation
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PROVIDER: PRJNA547712 | ENA |
REPOSITORIES: ENA
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Project description:The hypothalamus is a central regulator of many innate behaviors that are essential for survival, but the molecular mechanisms controlling hypothalamic patterning and cell fate specification remain poorly understood. To identify genes that control hypothalamic development, we have used single-cell RNA sequencing (scRNA-Seq) to profile mouse hypothalamic gene expression across 11 developmental time points between embryonic day 10 and postnatal day 45. This identified genes that delineated clear developmental trajectories for all major hypothalamic cell types and readily distinguished major regional subdivisions of the developing hypothalamus. We show that this approach can rapidly and comprehensively characterize mutants that control hypothalamic patterning and, in doing so, identify multiple genes that simultaneously repress posterior hypothalamic identity while promoting prethalamic identity. This argues in favor of a modified columnar organization of hypothalamus and prethalamus. These data serve as a resource for further studies of hypothalamic development, physiology, and dysfunction.
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Project description:Hypothalamic tanycytes, radial glial cells that share many features with neuronal progenitors, can generate small numbers of neurons in the postnatal hypothalamus, but the identity of these neurons and the molecular mechanisms that control tanycyte-derived neurogenesis are unknown. We report that tanycyte-specific disruption of the NFI family of transcription factors (Nfia/b/x) stimulates proliferation and tanycyte-derived neurogenesis. Single-cell RNA- and ATAC-Seq analysis reveals that NFI factors repress Shh and Wnt signaling in tanycytes, and small molecule inhibition of these pathways blocks proliferation and tanycyte-derived neurogenesis in Nfia/b/x-deficient mice. We show that Nfia/b/x-deficient tanycytes give rise to multiple mediobasal hypothalamic neuronal subtypes that can mature, integrate into hypothalamic circuitry, and selectively respond to changes in internal states. These findings identify molecular mechanisms controlling tanycyte-derived neurogenesis that can potentially be targeted to selectively remodel hypothalamic neural circuitry controlling homeostatic physiological processes.
2020-10-30 | GSE160377 | GEO
Project description:Hypothalamic tanycytes, radial glial cells that share many features with neuronal progenitors, can generate small numbers of neurons in the postnatal hypothalamus, but the identity of these neurons and the molecular mechanisms that control tanycyte-derived neurogenesis are unknown. We report that tanycyte-specific disruption of the NFI family of transcription factors (Nfia/b/x) stimulates proliferation and tanycyte-derived neurogenesis. Single-cell RNA- and ATAC-Seq analysis reveals that NFI factors repress Shh and Wnt signaling in tanycytes, and small molecule inhibition of these pathways blocks proliferation and tanycyte-derived neurogenesis in Nfia/b/x-deficient mice. We show that Nfia/b/x-deficient tanycytes give rise to multiple mediobasal hypothalamic neuronal subtypes that can mature, integrate into hypothalamic circuitry, and selectively respond to changes in internal states. These findings identify molecular mechanisms controlling tanycyte-derived neurogenesis that can potentially be targeted to selectively remodel hypothalamic neural circuitry controlling homeostatic physiological processes.
2020-10-30 | GSE160375 | GEO
Project description:The hypothalamus is a central regulator of many behaviors essential for survival such as temperature regulation, food intake and circadian rhythms. However, the molecular pathways that mediate hypothalamic development are largely unknown. To identify genes expressed in developing mouse hypothalamus, microarray analysis at 12 different developmental time points was performed. Developmental in situ hybridization was conducted for 1,045 genes dynamically expressed by microarray analysis. In this way, we identified markers that stably labeled each major hypothalamic nucleus over the entire course of neurogenesis, and thus constructed a detailed molecular atlas of the developing hypothalamus. As proof of concept for the utility of this data, we used these markers to analyze the phenotype of mice where Sonic Hedgehog (Shh) was selectively deleted from hypothalamic neuroepithelium, demonstrating an essential role for Shh in anterior hypothalamic patterning. Our results serve as a resource for functional investigations of hypothalamic development, connectivity, physiology, and dysfunction. Affymetrix MOE430 microarrays were used to analyze the expression patterns of mouse hypothalamic and preoptic area tissues. The results were compared across the variables of Strain, Sex and Age.
2010-05-27 | E-GEOD-21278 | biostudies-arrayexpress
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2016-05-04 | GSE72746 | GEO
Project description:The hypothalamus is a central regulator of many behaviors essential for survival such as temperature regulation, food intake and circadian rhythms. However, the molecular pathways that mediate hypothalamic development are largely unknown. To identify genes expressed in developing mouse hypothalamus, microarray analysis at 12 different developmental time points was performed. Developmental in situ hybridization was conducted for 1,045 genes dynamically expressed by microarray analysis. In this way, we identified markers that stably labeled each major hypothalamic nucleus over the entire course of neurogenesis, and thus constructed a detailed molecular atlas of the developing hypothalamus. As proof of concept for the utility of this data, we used these markers to analyze the phenotype of mice where Sonic Hedgehog (Shh) was selectively deleted from hypothalamic neuroepithelium, demonstrating an essential role for Shh in anterior hypothalamic patterning. Our results serve as a resource for functional investigations of hypothalamic development, connectivity, physiology, and dysfunction.
2010-05-04 | GSE21278 | GEO