Expression and characterization of the zebrafish orthologue of the human FOLR1 gene during embryogenesis.

ABSTRACT

It has been well established that many types of rapidly dividing normal and diseased cells require an increased amount of folate for DNA replication and repair as well as cellular metabolism. Thus one of folate's cognate receptors, Folate Receptor 1 (FOLR1) is usually up-regulated in rapidly dividing cells, including many types of cancerous tumors. Because zebrafish have become a model organism for understanding conserved vertebrate cellular pathways and human disease, there has been an increased need to identify and elucidate orthologous zebrafish genes that are central to known human maladies. The cells of all early animal embryos go through a phase of rapid division (cleavage) where particular cell cycle checkpoints are skipped until a specification event occurs directing these embryonic stem cells to their fated germ layer cell type. Interestingly, this rapid cell division that ignores cell cycle checkpoints is also observed in many cancers. Developing blastula and tumor cells both require folr1 expression to obtain folate. In this report we have identified the expression pattern of the zebrafish gene zgc165502, located on chromosome 15. Using computational and comparative methods and molecular biology techniques such as reverse transcription polymerase chain reaction (RT-PCR) and whole mount in situ hybridization (WISH) during embryogenesis, we demonstrate that zgc165502 is the zebrafish orthologue of the human FOLR1 gene. Understanding when and where FOLR1 orthologues are expressed in different biomedical model organisms such as the zebrafish will help researchers design better experiments to study the endogenous FOLR1 activity.