My lab is interested in mechanisms that regulate progenitor cells during development and regeneration. We focus on the skeletal system and muscle in the mouse and the zebrafish. More specifically, we study the mechanism of embryonic limb development in mice and heart and fin regeneration in zebrafish.
Limb development: Given that one out of 200 live births are associated with limb defects, studies of limb development are essential and directly related to understanding birth defects in humans. We are interested in how progenitor cells in the lateral plate mesoderm and/or early limb buds are regulated to initiate limb development, to undergo region-specific proliferation and differentiation in order to develop into each distinct skeletal element with unique shape at distinct location. Our specific focus includes functions of Sall genes, Isl1 and Irx genes, in relation to various signaling pathways, such as Hedgehog, fibroblast growth factor and Wnt/ß-catenin signaling.
Heart regeneration: Zebrafish possess remarkable ability to regenerate the heart from various experimental injuries through proliferation of de-differentiated cardiomyocytes. We are interested in mechanisms of local cardiomyocyte migration into the injured site, which we found essential for myocardial regeneration. We seek to understand how migration and proliferation of cardiomyocytes are coordinated to repair the heart, and what roles surrounding cell play in these processes.
Fin regeneration: Using zebrafish fin regeneration, we collaborated with a chemistry group and screened natural compounds and found novel compounds that stimulate or inhibit regeneration. Considering regeneration and cancer are yin and yang relationship of cellular activities, we collaborate with a cancer biology group to develop potential therapeutic compounds for cancer study.
Selected Publications (Pubmed Search)
Akiyama R, Kawakami H, Wong J, Oishi I, Nishinakamura R, and Kawakami Y. (2015) Sall4-Gli3 system in early limb progenitors is essential for the development of limb skeletal elements. Proc Natl Acad Sci USA. 112, 5075-5080.
Itou, J., Akiyama, R., Pehoski, S., Xiaodan Yu, Kawakami, H., and Kawakami, Y. (2014) Regenerative responses after mild heart injuries for cardiomyocyte proliferation in zebrafish Developmental Dynamics In press,
Kawakami, Y. (2013) Redefining the role of retinoic acid in limb development. Cell Reports 3, 1337-1338.
Akiyama, R., Kawakami, H., Taketo, M. M., Evans, S. M., Wada, W., Petryk, A., and Kawakami, Y. (2014) Distinct populations within Isl1 lineages contribute to appendicular and facial skeletogenesis through the ß-catenin pathway. Developmental Biology, 387, 37-48.
Itou, J., Oishi, I., Kawakami, H., Glass, T. J., Richter, J., Johnson, A., Lund, T. C. and Kawakami, Y. (2012) Migration of cardiomyocytes is essential for heart regeneration in zebrafish. Development, 139, 4133 – 4142.
Itou, J., Kawakami, H., Burgoyne, T. and Kawakami, Y. Life-long preservation of the regenerative capacity in the fin and heart in zebrafish. (2012) Biology Open, 1, 739 – 746.
Itou, J., Kawakami, H., Quach, T., Osterwalder, M., Evans, S. M., Zeller, R., and Kawakami, Y. (2012) Islet1 regulates establishment of the posterior hindlimb-field upstream of the Hand2-Shh morphoregulatory gene network in mouse embryos. Development 139, 1620 - 1629.
Kawakami Y*, Marti M., Kawakami H., Itou, J., Quach, T., Johnson, A., Sahara S., O’Leary D. D. M., Nakagawa Y., Lewandoski M., Pfaff S., Evans S. and Izpisua Belmonte J. C*. (2011) Islet1-mediated activation of the ß-catenin pathway is necessary for hindlimb initiation in mice. Development, 138, 4465 - 4473. *Co-corresponding authors
Kawakami Y., Uchiyama Y., Rodriguez-Esteban C, Inenaga T., Koyano-Nakagawa N., Kawakami H., Marti M., Kmita M., Monaghan-Nichols P., Nishinakamura R, Izpisua Belmonte J.C. (2009) Sall genes regulate region-specific morphogenesis in the mouse limb by modulating Hox activities. Development 136, 585-595.