Adult zebrafish are highly regenerative
Zebrafish organs carry out the same basic functions as mammalian organs, and are subject to similar disorders. Accordingly, human disease can be modeled in the zebrafish. Research groups have already begun using zebrafish to understand human hematological disorders, cancer and skeletal defects. Many diseases are linked by a common theme - tissue damage. For instance, Alzheimer's disease, heart failure, spinal cord injury, and diabetes are all caused by irreparable organ damage. While most human organs have an extremely limited ability to regenerate, zebrafish organs possess an elevated regenerative capacity, facilitating renewal of spinal cord, retina, appendages (fins), heart muscle, and potentially other tissues. Thus, zebrafish are susceptible to diseases found in humans, but also maintain a unique defense mechanism, regeneration. Our lab currently focuses on appendage and heart regeneration.
Fin regeneration
We will continue to apply forward and reverse genetic approaches to find new genes essential for perfect regeneration of the zebrafish tail fin. Fin regeneration is a very rapid process (~10-14 days) that replaces bone, epidermis, blood vessels, nerves, and connective tissue. To date, pilot screens and positional cloning strategies have revealed 4 genes essential for formation and function of the regeneration blastema, a proliferative structure crucial for fin regeneration in zebrafish and limb regeneration in certain amphibians. I expect that expanded screening efforts and candidate gene testing will uncover genes responsible for induction, proliferation, patterning, and completion of regeneration. Also, we have used inducible transgenic technology to detail how positional information in the appendage sets a defined level of Fgf signaling, and in doing so controls how fast new structures are replaced. We are further dissecting functions of Fgfs during fin regeneration, and have also branched out to investigate the roles of other developmental programs and regulatory mechanisms.
Heart regeneration
Recent discoveries of cardiac progenitor cells in mammals have exciting implications for cardiac biology and disease. Yet, it is unclear why they fail to support natural regeneration after myocardial infarction, an extremely common cause of human mortality and morbidity. Recently, we discovered that, by contrast with mammals, adult zebrafish regenerate heart muscle after major injury. Currently, we are investigating how progenitor cells for this new muscle arise and are coaxed toward successful regeneration. We are also defining the developmental response of non-myocardial cell types to injury, and their importance in heart regeneration.