RaxIs a Selector Gene for Mediobasal Hypothalamic Cell Types
RaxIs a Selector Gene for Mediobasal Hypothalamic Cell Types
The brain plays a central role in controlling energy, glucose, and lipid homeostasis, with specialized neurons within nuclei of the mediobasal hypothalamus, namely the arcuate (ARC) and ventromedial (VMH), tasked with proper signal integration. Exactly how the exquisite cytoarchitecture and underlying circuitry becomes established within these nuclei remains largely unknown, in part because hypothalamic developmental programs are just beginning to be elucidated. Here, we demonstrate that theRetina and anterior neural fold homeobox(Rax) gene plays a key role in establishing ARC and VMH nuclei in mice. First, we show thatRaxis expressed in ARC and VMH progenitors throughout development, consistent with genetic fate mapping studies demonstrating thatRax+ lineages give rise to VMH neurons. Second, the conditional ablation ofRaxin a subset of VMH progenitors using aShh::Credriver leads to a fate switch from a VMH neuronal phenotype to a hypothalamic but non-VMH identity, suggesting thatRaxis a selector gene for VMH cellular fates. Finally, the broader elimination ofRaxthroughout ARC/VMH progenitors usingSix3::Creleads to a severe loss of both VMH and ARC cellular phenotypes, demonstrating a role forRaxin both VMH and ARC fate specification. Combined, our study illustrates thatRaxis required in ARC/VMH progenitors to specify neuronal phenotypes within this hypothalamic brain region.Raxthus provides a molecular entry point for further study of the ontology and establishment of hypothalamic feeding circuits.
- University of Calgary Canada
- West Virginia University Institute of Technology United States
- The University of Texas at Austin United States
- Baylor College of Medicine United States
- Hotchkiss Brain Institute Canada
Homeodomain Proteins, Neurons, Gene Expression Regulation, Developmental, Hypothalamus, Middle, Mice, Transgenic, Mice, Animals, Cell Lineage, Eye Proteins, Signal Transduction, Transcription Factors
Homeodomain Proteins, Neurons, Gene Expression Regulation, Developmental, Hypothalamus, Middle, Mice, Transgenic, Mice, Animals, Cell Lineage, Eye Proteins, Signal Transduction, Transcription Factors
53 Research products, page 1 of 6
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
- 4
- 5
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).71 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
