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The anatomy of respiration

European scientists studied how malfunction of the respiratory centres in our brain could lead to breathing disorders. By identifying the molecular determinants of such respiratory conditions, they hope to design future intervention strategies.
The anatomy of respiration
Congenital central hypoventilation syndrome (CCHS) is a congenital condition in newborn babies that causes respiratory arrest during sleep. Although these breathing disorders are rare, they impose a great deal of suffering for affected families. Our limited understanding on the aetiology of these conditions stems from the difficulty in accessing and studying the neuronal populations that control respiration in the brainstem.

Accumulating evidence indicates that congenital breathing disorders are caused by malfunction of neuronal control of breathing. Particular parts of our brain are responsible for sensing oxygen and carbon dioxide in the periphery and relaying signals for the initiation of inspiration and respiration. Understanding how these respiratory centres emerge and function is central to comprehending CCHS aetiology.

With this in mind, scientists on the EU-funded 'Function of the transcription factors Olig3 and Lbx1 in brainstem respiratory nuclei' (OLIG3-LBX1 BREATHING) project focused on the role of certain transcription factors that function during development to establish the respiratory centres. The consortium worked on Olig3, a transcription factor that is expressed in progenitor cells of the dorsal brainstem and on Lbx1 a second transcription factor expressed in a hindbrain nucleus that controls breathing.

Mice carrying mutations in the Olig3 gene present with cyanosis shortly after birth although their breathing pattern is similar. However, Olig3 mutants fail to mature their breathing and hypoventilate. Anatomically, this is caused by the absence of the oxygen sensing centre, indicating the importance of the respiratory tract early in life. Similar observations were made using mice lacking another critical transcription factor, Tlx3.

By performing a genetic screen of CCHS patients, the consortium identified a mutation in a novel gene. They developed transgenic mice carrying the same mutation and noticed that their breathing was slower and shallower. Anatomical examination of these mice indicated that they lacked one breathing centre and could not sense or respond to carbon dioxide levels.

Collectively, these findings underscore the role of key transcription factors in the development of the brainstem respiratory centres. The identification that mutations in these transcription factors cause CCHS could form the basis for future research and intervention studies.

Related information


Respiratory centres, breathing disorders, congenital central hypoventilation syndrome, brainstem
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