Sensing trouble
The gene Atoh1 aids development of oxygen- and carbon dioxide- sensing cells essential for normal breathing and survival in newborn mice.
Breathing seems very simple: humans and other animals do it all the time without even thinking about it. Yet, many different cell types coordinate rhythmic breathing movements. Some cells set the breathing rhythm, motor neurons control the muscles, and other cells sense blood oxygen and carbon dioxide levels. Information about oxygen and carbon dioxide is necessary to trigger faster and deeper breaths when there is too little oxygen, for example, at high altitude. Or when there is too much carbon dioxide, for example, during exercise.
At birth, most newborns can breathe as fast as needed because key genes oversee the development of all the cells involved in breathing. Learning more about these genes and what they do could lead to better understanding of why some newborns are at risk for sudden infant death or crib death. The Atoh1 gene, for example, helps carbon dioxide-sensing cells called retrotrapezoid neurons develop. Mice born without the Atoh1 gene are unable to breathe normally and die at birth. But when the gene is only deleted from these carbon dioxide-sensing cells in mice, just half of them die. This suggests that Atoh1 in other cells may also be important for breathing.
Now, Van der Heijden and Zoghbi show that the Atoh1 gene also helps develop another set of cells that are essential for breathing called the parabrachial complex. These cells receive information from oxygen sensors and relay the information to cells that set breathing rhythms. Mice missing parabrachial complex cells do not breathe faster when oxygen levels in the air are low. Mice lacking Atoh1 from both the parabrachial complex cells and the retrotrapezoid cells have breathing problems and die at birth.
Van der Heijden and Zoghbi show that the Atoh1 gene is essential for two cell types that make mice breathe faster when oxygen or carbon dioxide levels change. Together these two cell types are necessary for survival. The experiments also may provide insights into what goes wrong in babies who experience sudden infant death. Mutations in genes that are important to both cell types increase the risk of these infant deaths. Newborn babies with mutations in such key developmental genes will be at risk when in low oxygen or high carbon dioxide environments because their breathing systems are still maturing.
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