The CHARGE syndrome gene chd-7 plays a role in dauer formation and longevity.

DIEGO MARTÍN JOFRÉ; DANE HOFFMAN; MCKENZIE GRUNDY; SIJUNG YUN; FRANCIS AMRIT GHANDI; DONNA BEER STOLZ; ESTEBAN SALVATORE; ARJUMAND GHAZI; JUDITH YANOWITZ; DANIEL HOCHBAUM

Conferencia; 23rd International C. elegans Conference; 2021

CHARGE syndrome is a complex developmental disorder caused by mutations in the chromodomain helicase DNA-binding protein-7 (Chd7) and characterized by retarded growth and malformations in the heart and nervous system tissues. However, despite the public health relevance of this disorder, relevant targets of CHD7 that relate to disease pathology are still poorly understood. Here we report that chd-7, the nematode ortholog of Chd7, is required for dauer morphogenesis, lifespan determination, and stress response. Genetic epistasis places chd-7 in the DAF-7/TGF-β pathway. Consistent with our discoveries, we found chd-7 to be allelic to scd-3, a previously identified dauer suppressor from the DAF-7/TGF-β pathway. Interestingly, DAF-12 transcriptionally regulates chd-7, which is necessary to repress daf-9 for execution of the dauer program. Transcriptomics analysis comparing chd-7?defective and normal dauers show multiple collagen genes, consistent with a conserved role for the TGF-β pathway in expression of the extracellular matrix. To validate a conserved function for chd-7 in vertebrates, we used Xenopus laevis embryos, an established model to study CHARGE syndrome?s features.