Nicole Jacobs, R. Craig Albertson
Abstract
Introduction: Humans are afflicted with spinal deformities that can impact their health and daily lives. Currently, the etiologies of most spinal deformities are unknown. Chromodomain helicase DNA binding protein 7 (chd7) and chd2 were recently implicated in spinal deformities in humans and mice, but little is known about the roles these genes play during spine development.
Objectives: Determine the roles of chd7 and chd2 in spinal development using the zebrafish Danio rerio as a model system.
Materials and Methods: Morpholino knockdown was used to determine the roles chd7 and chd2 play in early zebrafish development. In situ hybridization was performed to detect changes in expression of several prominent somitogenesis genes in zebrafish embryos with reduced translation of chd7 or chd2.
Results: Chd7 and chd2 morpholino injections produce similar phenotypes in zebrafish including curvature of the long axis of the body and pericardial edema, as well as other less prominent traits. Expression profiles of several genes involved in somite development and polarity are affected in chd7 morpholino injected embryos. The affects of chd2 morpholino knockdown on somitogenesis genes are currently being investigated.
Conclusion: Chd7 and chd2 play significant roles in somitogenesis in zebrafish. Reduced expression of both factors leads to disruption of the somitogenesis pathway and curvature of the long axis of the body.
Significance: Upon determination of the roles of chd7 and chd2 in spinal development, the information obtained regarding chd7 and chd2 function may offer molecular inroads into the etiology and pathophysiology of human spinal deformities.