Temporal cohesion of the structural, functional and molecular characteristics of the developing zebrafish heart

Abstract

Heart formation is a complex, dynamic and highly coordinated process of molecular, morphogenetic and functional factors with each interacting and contributing to formation of the mature organ. Cardiac abnormalities in early life can be lethal in mammals but not in the zebrafish embryo which has been widely used to study the developing heart. While early cardiac development in the zebrafish has been well characterized, functional changes during development and how these relate to architectural, cellular and molecular aspects of development have not been well described previously. To address this we have carefully characterised cardiac structure, function, cardiomyocyte proliferation and cardiac-specific gene expression between 48 and 120 hpf in the zebrafish. We show that the zebrafish heart increases in volume and changes shape significantly between 48 and 72 hpf accompanied by a 40% increase in cardiomyocyte number. Between 96 and 120 hpf, while external heart expansion slows, there is rapid formation of a mature and extensive trabecular network within the ventricle chamber. While ejection fraction does not change during the course of development other determinants of contractile function increase significantly particularly between 72 and 96 hpf leading to an increase in cardinal vein blood flow. This study has revealed a number of novel aspects of cardiac developmental dynamics with striking temporal orchestration of structure and function within the first few days of development. These changes are associated with changes in expression of developmental and maturational genes. This study provides important insights into the complex temporal relationship between structure and function of the developing zebrafish heart.

Differential expression of CARMIL‐family genes during zebrafish development

“…Expression appears at 72 hpf and is not seen at earlier time points, including 48 hpf. The zebrafish heart undergoes a morphological and functional change from a simple two-chambered tube-shaped organ at 48 hpf into a multi-layered and mature functioning organ by 120 hpf [Matrone et al, 2015]. …”

Working with zebrafish at postembryonic stages

“…Many other events occurring at postembryonic stages in zebrafish also resemble human fetal development, including modifications to the kidney (Drummond, 2005; Elizondo, Budi, & Parichy, 2010; Gerlach & Wingert, 2013) and gut (Crosnier et al, 2005; Wallace, Akhter, Smith, Lorent, & Pack, 2005); neurogenesis (Kizil, Kaslin, Kroehne, & Brand, 2012; Schmidt, Strahle, & Scholpp, 2013; Zupanc, 2011); ossification of axial and craniofacial bones (Bird & Mabee, 2003; Cubbage & Mabee, 1996; Elizondo et al, 2005; Kimmel, DeLaurier, Ullmann, Dowd, & McFadden, 2010); and continued, but differential, growth across the body (Parichy, Elizondo, Mills, Gordon, & Engeszer, 2009). Research focused on postembryonic stages has further made significant inroads toward understanding the development of the lateral line (Ghysen, Wada, & Dambly-Chaudière, 2014; Thomas, Cruz, Hailey, & Raible, 2015; Wada & Kawakami, 2015), pigment pattern (Kondo and Watanabe, 2015; Parichy & Spiewak, 2015; Singh & Nüsslein-Volhard, 2015), skeleton (Akiva et al, 2015; Eames et al, 2013), heart (Matrone, Wilson, Mullins, Tucker, & Denvir, 2015; Singleman & Holtzman, 2012), microbiome (Burns et al, 2015; Roeselers et al, 2011; Stephens et al, 2015), and lipid stores (Flynn, Trent, & Rawls, 2009; Minchin & Rawls, 2011). Investigating these and other postembryonic processes in zebrafish can lend critical insight into the conserved mechanisms by which postembryonic development occurs in humans.…”

Effects of Cyclin Dependent Kinase 9 inhibition on zebrafish larvae

“…We have shown that flavopiridol causes CDK9 inactivation as confirmed by Western blot analysis showing reduced phosphorylation of the Serine 2 (P-Ser2), the direct target of CDK9 27 . Chao and Price 16 found a similar result in Drosophila where they detected reduced 32 P-incorporated-RNA polymerase II following exposure to flavopiridol.…”