Open AccessThe CHARGE syndrome ortholog CHD-7 regulates TGF-β pathways in Caenorhabditis elegans
Author(s) -
Diego Martín Jofré,
Dane K. Hoffman,
Ailen S. Cervino,
Gabriella M Hahn,
McKenzie K Grundy,
Sijung Yun,
Francis Raj Gandhi Amrit,
Donna B. Stolz,
Luciana F Godoy,
Esteban Salvatore,
F Rossi,
Arjumand Ghazi,
M. Cecilia Cirio,
Judith L. Yanowitz,
Daniel Hochbaum
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2109508119
Subject(s) - biology , caenorhabditis elegans , xenopus , gene knockdown , microbiology and biotechnology , genetics , morpholino , signal transduction , rna binding protein , rna interference , messenger rna , rna , gene
Significance CHARGE syndrome is a complex developmental disorder caused by mutations in CHD7 (chromodomain helicase DNA-binding protein-7). We identifiedCaenorhabditis elegans chd-7 in a screen for suppressors of dauer formation, an alternative larval stage that develops under harsh environmental conditions. We foundchd-7 regulates tumor growth factor-β (TGF-β) signaling pathways both for dauer diapause and for development of the cuticle, a specialized extracellular matrix. In frog embryos, Chd7 promotes Col2a1 expression, which is necessary and sufficient to prevent CHARGE features. These studies establish a conserved role for Chd7 from worms to vertebrates in regulating the TGF-β signaling pathway. Genetic dissection ofchd-7 ’s role inC. elegans may help to define the molecular and cellular events that contribute to CHARGE syndrome.