Kenneth D. Poss, Ph.D.

(Biology, Massachusetts Institute of Technology)

Associate Professor, Cell Biology

Early Career Scientist, Howard Hughes Medical Institute

Regeneration in the zebrafish model system. It has been known for centuries that certain non-mammalian vertebrates, such as urodele amphibians and teleost fish, regenerate complex tissues much more effectively than mammals. Salamanders have long been the central characters employed in vertebrate regeneration studies. Two features make the teleost zebrafish a powerful, complementary model system to study organ regeneration. First, they are highly regenerative, equipped to regrow amputated fins, injured retinae, transected optic nerves and spinal cord, and resected heart muscle. Second, unlike salamanders, they are amenable to both forward and reverse genetic approaches. As is customary with genetic model systems, a wide array of community resources is available for gene discovery and molecular characterization in zebrafish, including mutagenesis screens, transgenesis, microarrays, developmental markers, and genome sequence information.

We are investigating the biology of spectacular regenerative events in zebrafish to discover new cellular mechanisms, and we are also developing new tools to interrogate regeneration deeply at the molecular level. Over the next several years, we will pursue fundamental aspects of organ regeneration—most importantly, how tissue renewal is stimulated by injury, and how newly created cells recognize position and functionally incorporate into existing tissue.

Heart regeneration. There is little or no natural regeneration of the major structural cells of the adult mammalian heart, the cardiomyocytes, after experimental injury paradigms. This regenerative deficiency is highly relevant to human disease, given that the number one cause of morbidity and mortality in the United States is ischemic myocardial infarction and scarring. Several years ago, we found that zebrafish regenerate cardiac muscle after removal of 20 percent of the ventricle, with little or no scarring. This unique model of cardiac injury and regeneration puts us in a great position to address an important question: How are new cardiac cells created and functionally integrated into an injured, contracting, adult heart?

It is a primary goal of our work to define the origin and developmental potential of cellular contributors to regenerated cardiac tissue. Toward this goal, we are developing myriad tools for lineage tracing in zebrafish. These technologies will also advance our field's ability to ask questions about gene function during heart regeneration at high spatiotemporal resolution. For example, we are exploring several fascinating questions regarding how epicardial cells, and generally the non-muscle cells that comprise the cardiac environment, respond to injury and facilitate regeneration. These avenues should yield clues to altering the regenerative capacity of the injured mammalian heart.

Fin regeneration. Zebrafish fins are external, transparent, nonvital, and highly organized structures, making them ideal for asking fundamental, high-resolution questions about complex tissue regeneration. Within two weeks after amputation of the caudal fin, a series of healing, proliferation, and patterning events replaces bone, epidermis, blood vessels, nerves, and connective tissue mesenchyme. We use forward and reverse genetic approaches to identify new regulatory mechanisms critical for appendage regeneration.

A hallmark of limb or fin regeneration is formation of the blastema, a proliferative mass of mesenchymal cells that is maintained as a zone of progenitor tissue for new structures. The central questions are these: (1) What cells give rise to the blastema, and how is its formation activated by injury? (2) How is blastemal activity maintained appropriately throughout regeneration? (3) How is the completion of regeneration remembered and enacted? An obvious strength of the zebrafish model system is the opportunity for mutagenesis screens. In our lab, we are currently screening to identify new regeneration genes, and we have expanded and modified our past approaches to identify greater numbers of interesting mutants.

During appendage regeneration in urodeles and teleosts, tissue replacement is meticulously regulated such that only the appropriate structures are recovered, a phenomenon referred to as positional memory. It is believed that there exists, or is quickly established after amputation, a gradient of positional information along the axes of the appendage that assigns region-specific instructions to injured tissue. We are identifying new candidate genes for maintaining positional memory, and we are using this information to direct reverse genetic approaches that will functionally define new regeneration and homeostasis genes.

Email
K.Poss@cellbio.duke.edu

349 Nanaline Duke Building, Box 3709
Duke University Medical Center
Durham, NC 27710

Telephone 919-681-8457
Fax 919-684-5481


Poss Lab Website

Selected Recent Publications
Gonzalez-Quevedo, R., Lee, Y., Poss, K. D., and Wilkinson, D. G. (2010). Neuronal regulation of the spatial patterning of neurogenesis. Developmental Cell 18, 136-147. -PDF-

Lee, Y., Hami, D., De Val, S., Kagermeier-Schenk, B., Wills, A. A., Black, B. L., Weidinger, G., and Poss, K. D. (2009). Maintenance of blastemal proliferation by functionally diverse epidermis in regenerating zebrafish fins. Developmental Biology 331, 270-280. -PDF-

Nachtrab, G. and Poss, K. D. (2009). Genetic DISC-section of regeneration in Drosophila. Developmental Cell 16, 777-778. -PDF-

Waxman, J. S., Keegan, B. R., Roberts, R. W., Poss, K. D., and Yelon D.  (2008)  Hoxb5b acts downstream of retinoic acid signaling in the forelimb field to restrict heart field potential in zebrafish.  Developmental Cell 15, 923-934. -PDF-

Marques, S., Lee, Y., Poss, K. D., and Yelon, D.  (2008) Reiterative roles for FGF signaling in the establishment of size and proportion of the zebrafish heart.  Developmental Biology 321, 397-406. -PDF-

Yin, V. and Poss, K. D.  (2008).  New regulators of vertebrate appendage regeneration.  Current Opinion in Genetics and Development 18, 381-386. -PDF-

Wills, A.A., Kidd, A.R., Lepilina, A., and Poss, K. D. (2008).  Fgfs control homeostatic regeneration in adult zebrafish fins. Development 135, 3063-3070. -PDF-

Yin, V., Thompson, J. M., Thummel, R., Hyde, D., Hammond, S., and Poss, K. D.  (2008).  Fgf dependent depletion of microRNA-133 promotes zebrafish appendage regeneration. Genes and Development 22, 728-733. -PDF-

Wills, A.A, Holdway, J.E., Major, R.J., Poss, K.D. (2008). Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafish. Development 135, 183-192. Epub 2007 Nov 28. -PDF-

Shin, D., Shin, C.H., Tucker, J., Ober, E., Rentzsch, F., Poss, K.D., Hammerschmidt, M., Mullins, M.C., and Stainier, D.Y.R. (2007). Bmp and Fgf signaling are essential for liver specification in zebrafish. Development 134, 2041-2050. -PDF-

Nechiporuk, A., Linbo, T., Poss, K.D., and Raible, D.W. (2007). Specification of epibranchial placodes in zebrafish. Development 134, 611-623. -PDF-

Poss, K.D. (2006). Getting to the heart of regeneration in zebrafish. Seminars in Cell and Developmental Biology 18, 36-45. -PDF-

Lepilina, A., Coon, A. N., Kikuchi, K., Holdway, J. E., Roberts, R. W., Burns, C. G., and Poss, K. D.  (2006). A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration.  Cell 127, 607-619.

Lee, Y., Grill, S., Sanchez, A., Murphy-Ryan, M., and Poss, K. D. (2005). Fgf signaling instructs position-dependent growth rate during zebrafish fin regeneration. Development 132, 5173-5183.

Poss KD. A zebrafish model of germ cell aneuploidy. Cell Cycle. 2004 Oct;3(10):1225-6. Epub 2004 Oct 13.

Poss, K. D., Nechiporuk, A., Stringer, K. F., Lee, C., and Keating, M. T. (2004). Germ cell aneuploidy in zebrafish with mutations in the mitotic checkpoint gene mps1. Genes and Development 18, 1527-1532.

Traver, D., Paw, B. H., Poss, K. D., Penberthy, W. T., Lin, S., and Zon, L. I. (2003). Transplantation and in vivo imaging of multilineage engraftment in zebrafish bloodless mutants. Nature Immunology 4, 1238-1246.

Poss, K. D., Keating, M. T., and Nechiporuk, A. (2003). Tales of regeneration in zebrafish. Developmental Dynamics 226, 202-210.

Nechiporuk, A., Poss, K. D., Johnson, S. L., and Keating, M. T. (2003). Positional cloning of a temperature-sensitive mutant emmental reveals a role for Sly1 during cell proliferation in zebrafish fin regeneration. Developmental Biology 258, 291-306.

Poss, K. D., Wilson, L. G., and Keating, M. T. Heart regeneration in zebrafish. (2002). Science 298, 2188-2190.

Poss, K. D., Nechiporuk, A., Hillam, A. M., Johnson, S. L., and Keating, M. T. (2002). Mps1 defines a proximal blastemal proliferative compartment essential for zebrafish fin regeneration. Development 129, 5141-5149.

Lab personnel
Jennifer Holdway (research tech)
Bridget Mayer (research tech)
Jim Burris (Zebrafish facility)
Amy Eastes (Zebrafish facility)
Wen-Yee Choi (postdoctoral fellow)
Yi Fang (postdoctoral fellow)
Kazu Kikuchi (postdoctoral fellow)
Jinhu Wang (postdoctoral fellow)
Viravuth Yin (postdoctoral fellow)
Matt Gemberling (graduate student)
Vikas Gupta (graduate student)
Greg Nachtrab (graduate student)
Sumeet Pal Singh (graduate student)
Christian Parobek (undergraduate student)