1. Math1 is essential for the development of hindbrain neurons critical for perinatal breathing.
- Author
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Rose MF, Ren J, Ahmad KA, Chao HT, Klisch TJ, Flora A, Greer JJ, and Zoghbi HY
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Cell Movement physiology, Glutamic Acid metabolism, Green Fluorescent Proteins genetics, Hypoventilation embryology, Hypoventilation physiopathology, In Vitro Techniques, Medulla Oblongata embryology, Medulla Oblongata physiology, Mice, Mice, Knockout, Mice, Transgenic, Neurogenesis physiology, Rhombencephalon cytology, Basic Helix-Loop-Helix Transcription Factors metabolism, Neurons physiology, Periodicity, Respiratory Mechanics physiology, Rhombencephalon embryology, Rhombencephalon physiology
- Abstract
Mice lacking the proneural transcription factor Math1 (Atoh1) lack multiple neurons of the proprioceptive and arousal systems and die shortly after birth from an apparent inability to initiate respiration. We sought to determine whether Math1 was necessary for the development of hindbrain nuclei involved in respiratory rhythm generation, such as the parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN), defects in which are associated with congenital central hypoventilation syndrome (CCHS). We generated a Math1-GFP fusion allele to trace the development of Math1-expressing pFRG/RTN and paratrigeminal neurons and found that loss of Math1 did indeed disrupt their migration and differentiation. We also identified Math1-dependent neurons and their projections near the pre-Bötzinger complex, a structure critical for respiratory rhythmogenesis, and found that glutamatergic modulation reestablished a rhythm in the absence of Math1. This study identifies Math1-dependent neurons that are critical for perinatal breathing that may link proprioception and arousal with respiration.
- Published
- 2009
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