Molecular chaperones are highly demanded in cells for protein homeostasis, especially in muscle cells. Our Previous studies demonstrated that Hsp90aa1.1, UNC-45b, and Smyd1b are essential for sarcomere assembly during myogenesis in zebrafish embryos. Deletion of any of them resulted in increased myosin protein degradation and embryonic lethality. However, little is known about the molecular chaperone events except for Hsp90aa1.1 and UNC-45b, which guide the stabilization of sarcomere protein to keep cellular homeostasis and their regulatory mechanism in muscle cells. To determine the function of Hsp90 co-chaperone, Aha1, in muscle development, I generated aha1a; aha1b double mutants in zebrafish using CRISPR. The results showed that Aha1a and Aha1b are intensely involved in stress response from heat shock and muscle defects but are dispensable in zebrafish muscle development and growth. Next, I defined gene expression changes induced by Smyd1b deficiency and their regulation using transcriptomics and a genetic approach. I found a dramatic muscle-specific upregulation of cytosolic hsp70, hsp90, and their co-chaperones was observed in smyd1b mutants by in situ hybridization. And the upregulated hsp70s is a common HSR shared in unc-45b and hsp90aa1.1 deficient embryo. I further demonstrated that these Hsp70s could interact with myosin partners, UNC-45b and Smyd1b, by Co-IP assay, and their upregulation depends on the transcriptional factor, heat shock factor 1 (Hsf1). Knockout of hsf1 blocked the upregulation of hsp70s expression in smyd1b deficient embryos. Finally, to study the function of the housekeeping Hsp70 (Hspa8), I generated hspa8 zebrafish mutants using CRISPR. hspa8 knockout mutants displayed a pharyngeal arch structure and myofibers loss in the craniofacial region. In addition, defective retinal ganglion cell differentiation and reduction of photoreceptors were detected in the eyes of hspa8 mutants. It appeared that hspa8 is critical for cell proliferation and survival during eye formation. Together, these studies provide novel insights into the expression and function of hsp70s in stress response and the essential role of hspa8 in craniofacial and eye development. Knowledge gained from these studies of chaperonopathies in the zebrafish model may help develop new strategies for treating chaperonopathies in human diseases.