Excitatory neurons of the proprioceptive, interoceptive, and arousal hindbrain networks share a developmental requirement for Math1.
Hindbrain networks important for sensation and arousal contain diverse neuronal populations with distinct projections, yet share specific characteristics such as neurotransmitter expression. The relationship between the function of these neurons, their developmental origin, and the timing of their migration remains unclear. Mice lacking the proneural transcription factor Math1 (Atoh1) lose neurons essential for hearing, balance, and unconscious proprioception. By using a new, inducible Math1(Cre*PR) allele, we found that Math1 is also required for the conscious proprioceptive system, including excitatory projection neurons of the dorsal column nuclei and for vital components of the interoceptive system, such as Barrington's nucleus, that is closely associated with arousal. In addition to specific networks, Math1 lineages shared specific neurotransmitter expression, including glutamate, acetylcholine, somatostatin, corticotropin releasing hormone, and nitric oxide. These findings identify twenty novel Math1 lineages and indicate that the Math1 network functions partly as an interface for conscious (early-born) and unconscious (late-born) proprioceptive inputs to the cortex and cerebellum, respectively. In addition, these data provide previously unsuspected genetic and developmental links between proprioception, interoception, hearing, and arousal.
Rose
Matthew F
MF
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Ahmad
Kaashif A
KA
Thaller
Christina
C
Zoghbi
Huda Y
HY
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001143:Arousal / Q000502:physiology*; D001306:Auditory Pathways / Q000196:embryology / Q000502:physiology; D001307:Auditory Perception / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018698:Glutamic Acid / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000196:embryology / Q000502:physiology; D009434:Neural Pathways / Q000196:embryology / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D011247:Pregnancy; D011434:Proprioception / Q000502:physiology*; D012249:Rhombencephalon / Q000196:embryology / Q000502:physiology*; D013004:Somatostatin / Q000378:metabolism
D000109:Acetylcholine; D051792:Basic Helix-Loop-Helix Proteins; D003346:Corticotropin-Releasing Hormone; D018698:Glutamic Acid; D007980:Levodopa; D009569:Nitric Oxide; D013004:Somatostatin; C500943:Atoh1 protein, mouse