The vertebrate body undergoes an amazing process of growth during early development to form the trunk and tail of the body.  In zebrafish, this happens within the first 24 hours of development.  Zebrafish, like all vertebrates, grow from the neck down by the progressive addition of cells from a progenitor population located at the most posterior end of the embryo, which contributes cells to both the mesodermal (muscle and bone) and neural (spinal cord) tissues.  A major interest in the lab is to understand the mechanisms that regulate this process.  Our principal focus is on the signaling factors that pattern and regulate the mesodermal progenitors, including Wnts, Fgfs, Bmps, Nodals and retinoic acid, and their interaction with transcription factors that regulate the progenitors, particularly members of the T-box family.  For example (Szeto and Kimelman, 2006), we demonstrated that the position of the mesodermal progenitors along the body is regulated by a combination of Nodal and Bmp signals, which regulate a clock that tells the mesodermal progenitors when to commit to differentiation.   We showed (Martin and Kimelman, 2008) that an autoregulatory loop involving the Brachyury family of T-box transcription factors (No tail and Bra) and the Wnt signaling factors is required to maintain the mesodermal progenitors in an active state. We proposed (Martin and Kimelman, 2009) that this autoregulatory loop was a vertebrate creation, that allowed the progenitors to stay active for long times, permitting the formation of diverse body types.  Our current research involves the production of transgenic zebrafish that will allow us to understand how the fate and proliferation of the mesodermal progenitors is regulated, taking advantage of the excellent optical properties of the transgenic zebrafish and the ability to transplant cells between embryos.

During and after gastrulation, the vertebrate embryo undergoes dramatic morphological changes to form the final body plan.  One of these morphological transformations involves a process called convergence & extension, which moves the mesodermal cells into their final position in the embryo.  We found (Weiser et al., 2007) found that a scaffolding protein called Gravin regulates a major change in the cells from convergence (migratory behavior) to extension (intercalative behavior).  We also showed that a myosin phosphatase, Mypt1, plays a central role in the convergence behavior of cells by regulating the type of protrusions they use to locomote (Weiser et al., 2009).  We are currently studying the morphogenetic behavior controlled by a T-box transcription factor called Spadetail.  In the fascinating spadetail mutant, cells that should give rise to the muscles and bone of the trunk end up stuck at the most posterior end of the embryo due to changes in the morphogenesis of these cells, forming a large bolus of cells called the “spade”.