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Sustained Hox5 gene activity is required for respiratory motor neuron development
Polyxeni Philippidou1, Carolyn M Walsh, Josée Aubin
1Howard Hughes Medical Institute, New York University School of Medicine, Smilow Neuroscience Program, Department of Physiology and Neuroscience, New York, New York, USA.
Nature Neuroscience
|October 30, 2012
Summary
Two Hox genes, Hoxa5 and Hoxc5, are crucial for phrenic motor column (PMC) development and diaphragm innervation in mammals. Their absence causes respiratory failure by disrupting PMC organization and branching, essential for breathing.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Mammalian respiration depends on phrenic motor column (PMC) neurons that innervate the diaphragm.
- The molecular mechanisms governing PMC development and connectivity remain largely uncharacterized.
Purpose of the Study:
- To investigate the role of Hox genes in the development and function of the phrenic motor column (PMC).
- To elucidate the specific contributions of Hoxa5 and Hoxc5 to PMC identity, organization, and innervation.
Main Methods:
- Utilized mouse models with genetic deletions of Hox genes in motor neurons.
- Analyzed PMC development, including neuronal survival, columnar organization, and axonal branching patterns.
- Investigated the temporal requirements of Hox gene function through late gene removal experiments.
Main Results:
- Hoxa5 and Hoxc5 are essential for PMC clustering, intramuscular branching, and neuronal survival.
- Loss of Hox5 genes in motor neurons leads to failed axonal arborization and respiratory failure, independent of cell death.
- Late removal of Hox5 genes impairs PMC number and branching, indicating a continuous requirement for Hox function.
Conclusions:
- Hox5 genes orchestrate phrenic motor column (PMC) development through distinct, temporally regulated wiring programs.
- These findings reveal a critical role for Hox genes in establishing the precise connectivity required for breathing.
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