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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation

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Rax is a selector gene for mediobasal hypothalamic cell types.

Fuqu Lu¹, Deepon Kar, Nicole Gruenig

¹Department of Medical Genetics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience

|January 4, 2013

Summary

The Retina and anterior neural fold homeobox (Rax) gene is crucial for developing specific brain nuclei controlling energy balance. Rax specifies neuronal fates in the arcuate (ARC) and ventromedial (VMH) hypothalamus.

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Published on: September 20, 2021

Area of Science:

Neuroscience
Developmental Biology
Genetics

Background:

The brain, particularly the hypothalamus, regulates energy, glucose, and lipid homeostasis.
Specialized neurons in the arcuate (ARC) and ventromedial (VMH) nuclei integrate metabolic signals.
The developmental mechanisms establishing hypothalamic nuclei are not fully understood.

Purpose of the Study:

To investigate the role of the Retina and anterior neural fold homeobox (Rax) gene in the development of ARC and VMH nuclei.
To determine if Rax acts as a selector gene for VMH neuronal fates.
To elucidate Rax's function in specifying neuronal phenotypes within the mediobasal hypothalamus.

Main Methods:

Examined Rax expression patterns in developing mouse hypothalamus using genetic fate mapping.
Utilized conditional gene ablation of Rax in VMH progenitors (Shh::Cre).
Performed broader Rax elimination in ARC/VMH progenitors (Six3::Cre).

Main Results:

Rax is expressed in ARC and VMH progenitors throughout development.
Rax+ lineages give rise to VMH neurons.
Conditional Rax ablation in VMH progenitors caused a switch to non-VMH hypothalamic identity.
Widespread Rax elimination severely reduced both VMH and ARC neuronal phenotypes.

Conclusions:

Rax is essential for specifying neuronal phenotypes in ARC and VMH progenitors.
Rax acts as a key selector gene for VMH cellular fates.
Rax provides a molecular target for studying hypothalamic feeding circuit development.