Martha Marvin, Biology

Small heat shock proteins are necessary for heart migration and laterality determination in zebrafish

Jamie L. Lahvic a,1, Yongchang Ji b, Paloma Marin a, Jonah P. Zuflacht a,2, Mark W. Springel a,3, Jonathan E. Wosen a, Leigh Davis a,4, Lara D. Hutson a,5, Jeffrey D. Amack b,
Martha J. Marvina,*

a Williams College Department of Biology, 59 Lab Campus Drive, Williamstown, MA 01267, USA
b Department of Cell and Developmental Biology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA

Small heat shock proteins (sHsps) regulate cellular functions not only under stress, but also during normal development, when they are expressed in organ-specific patterns. Here we demonstrate that two small heat shock proteins expressed in embryonic zebrafish heart, hspb7 and hspb12, have roles in the development of left–right asymmetry. In zebrafish, laterality is determined by the motility of cilia in Kupffer’s vesicle (KV), where hspb7 is expressed; knockdown of hspb7 causes laterality defects by disrupting the motility of these cilia. In embryos with reduced hspb7, the axonemes of KV cilia have a 9þ0 structure, while control embyros have a predominately 9þ2 structure. Reduction of either hspb7 or hspb12 alters the expression pattern of genes that propagate the signals that establish left–right asymmetry: the nodal-related gene southpaw (spaw) in the lateral plate mesoderm, and its downstream targets pitx2, lefty1 and lefty2. Partial depletion of hspb7 causes concordant heart, brain and visceral laterality defects, indicating that loss of KV cilia motility leads to coordinated but randomized laterality. Reducing hspb12 leads to similar alterations in the expression of downstream laterality genes, but at a lower penetrance. Simultaneous reduction of hspb7 and hspb12 randomizes heart, brain and visceral laterality, suggesting that these two genes have partially redundant functions in the establishment of left–right asymmetry. In addition, both hspb7 and hspb12 are expressed in the precardiac mesoderm and in the yolk syncytial layer, which supports the migration and fusion of mesodermal cardiac precursors. In embryos in which the reduction of hspb7 or hspb12 was limited to the yolk, migration defects predominated, suggesting that the yolk expression of these genes rather than heart expression is responsible for the migration defects.

 J.L. Lahvic et al. / Developmental Biology 384 (2013) 166–180