Teashirt 3 regulates development of neurons involved in both respiratory rhythm and airflow control

J Neurosci. 2010 Jul 14;30(28):9465-76. doi: 10.1523/JNEUROSCI.1765-10.2010.


Neonatal breathing in mammals involves multiple neuronal circuits, but its genetic basis remains unclear. Mice deficient for the zinc finger protein Teashirt 3 (TSHZ3) fail to breathe and die at birth. Tshz3 is expressed in multiple areas of the brainstem involved in respiration, including the pre-Bötzinger complex (preBötC), the embryonic parafacial respiratory group (e-pF), and cranial motoneurons that control the upper airways. Tshz3 inactivation led to pronounced cell death of motoneurons in the nucleus ambiguus and induced strong alterations of rhythmogenesis in the e-pF oscillator. In contrast, the preBötC oscillator appeared to be unaffected. These deficits result in impaired upper airway function, abnormal central respiratory rhythm generation, and altered responses to pH changes. Thus, a single gene, Tshz3, controls the development of diverse components of the circuitry required for breathing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biological Clocks / physiology
  • Calcium / metabolism
  • Electrophysiology
  • Mice
  • Mice, Transgenic
  • Motor Neurons / physiology*
  • Nerve Net / growth & development
  • Nerve Net / metabolism*
  • Pulmonary Ventilation / physiology*
  • Respiration*
  • Respiratory Center / physiology
  • Rhombencephalon / growth & development
  • Rhombencephalon / metabolism*
  • Statistics, Nonparametric
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Work of Breathing / physiology*


  • Teashirt 3 protein, mouse
  • Transcription Factors
  • Calcium