Math1 is essential for the development of hindbrain neurons critical for perinatal breathing.
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.
Rose
Matthew F
MF
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Ren
Jun
J
Ahmad
Kaashif A
KA
Chao
Hsiao-Tuan
HT
Klisch
Tiemo J
TJ
Flora
Adriano
A
Greer
John J
JJ
Zoghbi
Huda Y
HY
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D007040:Hypoventilation / Q000196:embryology / Q000503:physiopathology; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000196:embryology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010507:Periodicity; D015656:Respiratory Mechanics / Q000502:physiology*; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology* / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D018698:Glutamic Acid; D049452:Green Fluorescent Proteins; C500943:Atoh1 protein, mouse