dB2 neuron dysfunction causes congenital hypoventilation

Congenital hypoventilation encompasses a series of life-threatening respiratory disorders that are classically diagnosed in newborns. These conditions are characterized typically by hypoventilation, apnea, and insensitivity to elevated levels of arterial PCO2. Mutations in the transcription factors PHOX2B or LBX1 correlate with congenital central hypoventilation disorders, but the dysfunctional neurons responsible for these respiratory diseases are unknown. During my studies, I investigated the function of a molecular defined neural type of medullary neurons that co-express both factors, that is the dB2 neurons. My work shows that distinct subgroups of dB2 neurons account for respiratory dysfunctions and phenotypic manifestations observed in congenital hypoventilation. By combining intersectional labeling, murine intersectional chemogenetics, lineage-tracing, and conditional mutagenesis, my doctoral investigation reveals that specific subgroups of dB2 neurons are crucial for i) regulating respiratory tidal volumes, ii) modulating the hypercarbic reflex and iii) ensuring neonatal respiratory stability. My work provides functional evidence for the critical role of medullary dB2 neurons in neonatal respiratory physiology. In summary, my work uncovers novel components of the central circuit regulating breathing homeostasis and establishes dB2 neuron dysfunction to be causative in congenital hypoventilation.

Author dc:creator

• Xia, Yiling

• congenital hypoventilation
• dB2 neurons
• breathing homeostasis

Licence dc:rights.uri

• http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen

Language dc:language

eng

Identifier URI

http://dx.doi.org/10.17169/refubium-47004

OAI record oai:identifier

https://refubium.fu-berlin.de/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Arefubium.fu-berlin.de%3Afub188%2F47286