Transcription factors governing the development of GHRH-neurons
Transcription factors governing the development of GHRH-neurons
批准号:
10201931
负责人:
JAE W LEE
金额:
$55.83万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-08-15 至 2021-07-31
关键词:
AreaBindingBiochemicalCellsChIP-seqDataData SetDevelopmentDevelopmental GeneDwarfismEmbryoEmbryonic DevelopmentEnsureFOXP2 geneGenesGoalsGrowthGrowth and Development functionHomeostasisHypothalamic structureImmunohistochemistryIn Situ HybridizationIndividualKnockout MiceLifeLinkMapsMetabolic DiseasesMethodsMolecularMusNeuronsPathway interactionsPatternPhysiologicalPlayProcessProductionRegulationRegulator GenesRegulatory PathwayReportingReproductionResearchResearch Project SummariesRoleSomatotropin-Releasing HormoneStructure of nucleus infundibularis hypothalamiTestingTimeWorkcell typechromatin immunoprecipitationconditional knockoutenergy balanceexperimental studyfeedingfight againstgenome-widegenome-wide analysisimprovedin vivoinnovationmouse geneticsmouse genomemouse modelneuron developmentnovelpostnatalprogenitorprogramssingle-cell RNA sequencingtranscription factortranscriptome
中文摘要
项目总结
英文摘要
Project Summary
The research goal of Lee lab is to decipher the gene regulatory network that directs the embryonic development
of various types of neurons in the mouse arcuate nucleus of the hypothalamus (ARC). Neurons in the ARC
centrally regulate various homeostatic processes critical for survival and reproduction. Despite extensive studies
on the physiological roles of ARC neurons, the gene regulatory programs for their development are poorly
understood. Lee lab has been pioneering this challenging area of studies by successfully combining mouse
genetics and genome-wide studies. In particular, Lee lab accomplished the first ChIP-Seq (for chromatin
immunoprecipitation followed by sequencing) and scRNA-Seq (for single cell RNA-Seq) analyses with
developing ARC. Interestingly, many ARC neurons share common developmental lineages. This is likely to be
critical to ensure the balanced production of different ARC neurons during embryogenesis, enabling a highly
coordinated regulation of various homeostatic processes in later postnatal life, such as integration of feeding,
reproduction, and growth. By performing scRNA-Seq with E15 ARC, when ARC neurons actively develop, Le
lab identified transcription factors that are highly likely to play critical roles in the development of ARC neurons.
These include the TFs Dlx1/2 and Prox1, which are hypothesized to play vital roles in establishing GHRH-
neuronal fate over other related ARC neuronal lineages. By testing this hypothesis using an ensemble of
biochemical and cellular methods, mouse genetics and genome-wide approaches, Lee lab wishes to advance
the understanding of how common progenitors are guided to take a specific linage over other related ARC
neuronal fates, resulting in the balanced development of various ARC neuronal types during embryogenesis.
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Transcription Factors Governing the Development of GHRH-neurons
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