Loss of <i>Atoh1</i> from neurons regulating hypoxic and hypercapnic chemoresponses causes neonatal respiratory failure in mice.

Abstract

<i>Atoh1</i>-null mice die at birth from respiratory failure, but the precise cause has remained elusive. Loss of <i>Atoh1</i> from various components of the respiratory circuitry (e.g. the retrotrapezoid nucleus (RTN)) has so far produced at most 50% neonatal lethality. To identify other <i>Atoh1</i>-lineage neurons that contribute to postnatal survival, we examined parabrachial complex neurons derived from the rostral rhombic lip (rRL) and found that they are activated during respiratory chemochallenges. <i>Atoh1</i>-deletion from the rRL does not affect survival, but causes apneas and respiratory depression during hypoxia, likely due to loss of projections to the preBötzinger Complex and RTN. <i>Atoh1</i> thus promotes the development of the neural circuits governing hypoxic (rRL) and hypercapnic (RTN) chemoresponses, and combined loss of <i>Atoh1</i> from these regions causes fully penetrant neonatal lethality. This work underscores the importance of modulating respiratory rhythms in response to chemosensory information during early postnatal life.