In Drosophila, atonal encodes a basic helix-loop-helix (bHLH) protein essential for the development of chordotonal organs (sensory organs for proprioception, balance and audition). The mouse atonal homolog 1 (Math1) is expressed in the hindbrain, dorsal neural tube, inner ear, Merkel cells, and joints. Gene targeting in mice revealed that Mah1 is essential for the genesis of cerebellar granule neurons and inner ear hair cells. Furthermore, Math1 null nice die shortly after birth because of inability to breathe. To investigate the influence of Math1 on the differentiation of neurons involved in respiratory control, we will assess the neurophysiological integrity of the respiratory circuitry in Math1 null embryos, fate-map embryonic brainstem neurons that express Math1 null newborns die quickly, we will also target atonal into the Math1 locus to ascertain which facets of the phenotype can be rescued. Complete rescue will identify the bHLH domain as the mediator of Math1 function; partial rescue will indicate that other portions of the protein are necessary in the mammal. These data will allow future analysis of molecular interactions in the development of the brainstem, cerebellum and inner ear hair cells, with ramifications for understanding cerebellar anomalies, deafness, balance disorders, and neonatal breathing dysfunctions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31MH012444-02
Application #
6185509
Study Section
Special Emphasis Panel (ZRG1-MDCN-6 (01))
Program Officer
Goldschmidts, Walter L
Project Start
2000-09-01
Project End
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
2
Fiscal Year
2000
Total Cost
$24,394
Indirect Cost
Name
Baylor College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Shroyer, Noah F; Helmrath, Michael A; Wang, Vincent Y-C et al. (2007) Intestine-specific ablation of mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis. Gastroenterology 132:2478-88
Fritzsch, B; Matei, V A; Nichols, D H et al. (2005) Atoh1 null mice show directed afferent fiber growth to undifferentiated ear sensory epithelia followed by incomplete fiber retention. Dev Dyn 233:570-83