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Transcription factor mesenchyme homeobox protein 2 (MEOX2) modulates nociceptor function
Tomislav Kokotović1,2,3, Ewelina M Lenartowicz1, Michiel Langeslag4,5,6
1Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.
The FEBS Journal
|January 14, 2022
Summary
Mesenchyme homeobox protein 2 (MEOX2) is crucial for pain perception. Its reduced expression in mice impairs action potential initiation in sensory neurons, affecting pain signaling.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Mesenchyme homeobox protein 2 (MEOX2) is a transcription factor vital for mesoderm development.
- Dysregulation of MEOX2 is implicated in Congenital Insensitivity to Pain.
- The Drosophila homologue of MEOX2, btn, influences nocifensive responses.
Purpose of the Study:
- To investigate the role of MEOX2 in the mammalian peripheral nervous system, specifically in nociception.
- To characterize the function of MEOX2 in sensory neurons using a Meox2 heterozygous mouse model.
Main Methods:
- Utilized a Meox2 heterozygous mouse model (Meox2+/-).
- Conducted behavioral, cellular, and electrophysiological analyses of sensory nervous system function.
- Performed gene expression analysis, including transcriptomics of dorsal root ganglia (DRG).
Main Results:
- MEOX2 is expressed in mouse DRG and spinal cord, localizing to sensory neuron nuclei.
- Meox2+/- mice exhibited altered nociception, including impaired action potential initiation.
- Decreased expression of Scn9a and Scn11a (encoding Nav1.7 and Nav1.9 channels) and downregulation of pain-associated genes (PENK, NPY) were observed.
Conclusions:
- MEOX2 plays a novel role in primary afferent nociceptor neurons.
- MEOX2 is essential for maintaining the transcriptional program required for acute and inflammatory pain perception.
- MEOX2 influences the expression of key genes involved in neuronal excitability and pain signaling.
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