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Journal of Neuroscience
Article . 2013 . Peer-reviewed
License: CC BY NC SA
Data sources: Crossref
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RaxIs a Selector Gene for Mediobasal Hypothalamic Cell Types

Authors: Deborah M. Kurrasch; Eric C. Swindell; Fuqu Lu; Carol Schuurmans; Nicole Gruenig; Zi Wei Zhang; Peter H. Mathers; +4 Authors

RaxIs a Selector Gene for Mediobasal Hypothalamic Cell Types

Abstract

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.

Keywords

Homeodomain Proteins, Neurons, Gene Expression Regulation, Developmental, Hypothalamus, Middle, Mice, Transgenic, Mice, Animals, Cell Lineage, Eye Proteins, Signal Transduction, Transcription Factors

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    71
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    Top 10%
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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).
BIP!Citations provided by BIP!
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.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
71
Top 10%
Top 10%
Top 10%
hybrid