Fer Kinase is Required for Proper Vasculogenesis in Zebrafish
Dr. Aaron Putzke
Fer kinase, a protein involved in the regulation of cell-cell adhesion and proliferation, has been implicated in leukemia, gastric cancer, and liver cancer. However, the role Fer plays in the molecular mechanisms of these diseases remains largely unknown. By studying Fer during development, we hope to obtain a better understanding of its involvement in human carcinogenesis. Our lab has shown that FRK-1, a Fer kinase homologue in C. elegans, is involved in regulating a stem cell-like population during development. In this study, we begin to bridge the gap between the invertebrate and vertebrate realms by elucidating the role that Fer kinase plays during zebrafish embryogenesis. Our data indicate that not only is a Fer homologue expressed in zebrafish, but that it is required for normal vaculogenesis and hematopoiesis. Fer mRNA is expressed in the early hematopoietic stem cell lineage by 24 hpf, peaks at 48 hpf and is absent by 72 hpf. Morpholino knock-down of Fer results in disorganized vasculature and reduced sprouting of intersegmental vessels, which ultimately leads to improper circulation. Finally, we have performed quantitative gene expression and embryonic rescue experiments implicating Fer regulation of the Wnt-Notch pathway, which directs the ratio of vascular/blood cells as well as angiogenesis during development. This unique regulatory function for Fer kinase would provide valuable information not only to the field of developmental biology, but could also lead to novel therapies in a variety of cancers in which expression of Fer kinase is either misregulated or deleted, such as in myeloid leukemia.
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