title: Small heat shock proteins Hspb7 and Hspb12 regulate early steps of cardiac morphogenesis.
abstract: Cardiac morphogenesis is a complex multi-stage process, and the molecular basis for controlling distinct steps remains poorly understood. Because gata4 encodes a key transcriptional regulator of morphogenesis, we profiled transcript changes in cardiomyocytes when Gata4 protein is depleted from developing zebrafish embryos. We discovered that gata4 regulates expression of two small heat shock genes, hspb7 and hspb12, both of which are expressed in the embryonic heart. We show that depletion of Hspb7 or Hspb12 disrupts normal cardiac morphogenesis, at least in part due to defects in ventricular size and shape. We confirmed that gata4 interacts genetically with the hspb7/12 pathway, but surprisingly, we found that hspb7 also has an earlier, gata4-independent function. Depletion perturbs Kupffer's vesicle (KV) morphology leading to a failure in establishing the left-right axis of asymmetry. Targeted depletion of Hspb7 in the yolk syncytial layer is sufficient to disrupt KV morphology and also causes an even earlier block to heart tube formation and a bifid phenotype. Recently, several genome-wide association studies found that HSPB7 SNPs are highly associated with idiopathic cardiomyopathies and heart failure. Therefore, GATA4 and HSPB7 may act alone or together to regulate morphogenesis with relevance to congenital and acquired human heart disease.
authors.affiliation: Department of Surgery, Weill Cornell Medical College, NY 10065, USA.
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Rosenfeld
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Mercer
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Mason
authors.forename: Todd
authors.initials: T
authors.lastname: Evans
mesh_terms: D000818:Animals; D019521:Body Patterning; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006352:Heart Ventricles / Q000254:growth & development / Q000378:metabolism; D050888:Heat-Shock Proteins, Small / Q000235:genetics / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism; D009024:Morphogenesis; D060172:Morpholinos / Q000008:administration & dosage; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D015533:Transcriptional Activation; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050980:GATA Transcription Factors; C525957:Gata4 protein, zebrafish; D050888:Heat-Shock Proteins, Small; D060172:Morpholinos; D029961:Zebrafish Proteins
keywords: Cardiogenesis; Gata4; Heart development; Kupffer's vesicle; YSL; Zebrafish