We seek to understand the mechanisms that regulate development of cells and coordinate those cells into functional systems in the animal body.
Stem cells are characterized by their self-renewal and the ability to differentiate into specialized cell types. During differentiation, a variety of progenitor cells that are in transition to specialized cell types are generated. How are specific cell types generated and organized into functional organs? We ask this question by studying the mechanisms of development and regeneration using cell culture and animal models (mice and zebrafish). More specifically, we aim to understand how various progenitor cells are generated, how they differentiate and how they undergo morphogenesis during embryonic development. We also aim to understand how dormant genetic systems are regulated for damaged organs to regenerate or for tissues to be maintained in adult animals.
Stem cells in the adult body are central to tissue renewal and regeneration. Humans have limited ability to regenerate tissues/organs after damage; however, certain animals, such as zebrafish, possess remarkable ability to regenerate various organs. We study the mechanisms that regulate regeneration of the fin and heart in zebrafish.
Congenital limb malformations are one of most common human disorders, and occur in one in 1,000 live births. Patterning and proliferation of progenitor cells of limb buds during embryonic development results in the development of each skeletal element with unique shape and size, located at a defined position. Abnormal limb development caused by genetic mutations or teratogenic effects leads to malformations with abnormal, loss of, or additional skeletal elements. Moreover, up to 18% of children with a congenital limb malformation die before 6 years of age due to associated malformations and/or dysfunctions of other organs. Therefore, understanding the mechanisms of limb development is relevant not only to basic science, but also to human health and medicine. We study the mechanisms bu which select transcription factors, signaling pathways and cellular metabolic activities regulate limb progenitors.
Another aspect of progenitor cell development/differentiation in the embryo is body elongation. At the end of gastrulation, which generates three germ layers (ectoderm, endoderm, mesoderm), vertebrate embryos develop only the head and anterior structures at the cervical level. Various types of progenitor cells, located at the caudal end of the body undergo proliferation, differentiation and migration to progressively add new body parts. We aim to understand how bi-potential neuromesodermal progenitors self-renew and generate mesodermal and neural progenitors in a balanced manner. We also study how nascent mesodermal progenitors further undergo differentiation and migration for proper body development.
Selected Publications: PubMed Search
Gata6 restricts Isl1 to the posterior of nascent hindlimb buds through Isl1 cis-regulatory modules. Tahara N, Akiyama R, Theisen JWM, Kawakami H, Wong J, Garry DJ, Kawakami Y. Developmental Biology. 2018; 434(1):74-83.
Gata6-Dependent GLI3 Repressor Function is Essential in Anterior Limb Progenitor Cells for Proper Limb Development. Hayashi S, Akiyama R, Wong J, Tahara N, Kawakami H, Kawakami Y. PLoS Genetics. 2016; 12(6):e1006138.
Sall4-Gli3 system in early limb progenitors is essential for the development of limb skeletal elements. Akiyama R, Kawakami H, Wong J, Oishi I, Nishinakamura R, Kawakami Y. Proceedings of the National Academy of Sciences of the United States of America. 2015; 112(16):5075-80.
Regenerative responses after mild heart injuries for cardiomyocyte proliferation in zebrafish. Itou J, Akiyama R, Pehoski S, Yu X, Kawakami H, Kawakami Y. Developmental Dynamics. 2014; 243(11):1477-86.
Migration of cardiomyocytes is essential for heart regeneration in zebrafish. Itou J, Oishi I, Kawakami H, Glass TJ, Richter J, Johnson A, Lund TC, Kawakami Y. Development. 2012; 139(22):4133-42.
Islet1 regulates establishment of the posterior hindlimb field upstream of the Hand2-Shh morphoregulatory gene network in mouse embryos. Itou J, Kawakami H, Quach T, Osterwalder M, Evans SM, Zeller R, Kawakami Y. Development. 2012; 139(9):1620-9.
Islet1-mediated activation of the β-catenin pathway is necessary for hindlimb initiation in mice. Kawakami Y, Marti M, Kawakami H, Itou J, Quach T, Johnson A, Sahara S, O'Leary DD, Nakagawa Y, Lewandoski M, Pfaff S, Evans SM, Izpisua Belmonte JC. Development. 2011; 138(20):4465-73.