Description:

We are exploring the profound roles of ion fluxes during two vertebrate developmental stages: the establishment and patterning of the left-right (LR) axis during early embryogenesis, and the regeneration of skin, muscle, skeleton, and spinal cord during regeneration of an amputated appendage. (See related project >>) Both of these processes are fascinating as questions, and critically important for guiding the design of biomedical approaches to, in the case of LR patterning, correct birth defects (such as Hypoplastic Left Heart Syndrome, heterotaxy, asplenia, polysplenia, transposition of the major blood vessels, situs inversus, etc.) which together affect more than 1 in 8000 births, and in the case of regeneration, to replace diseased or damaged tissue by harnessing the body's latent ability to recreate tissue.

Progress

We have implicated the movement of the neurotransmitter serotonin among cells (via specific transporters and directly via gap junctions), long before neurons appear, as a key signal that allows embryos to align the left-right axis. This is directly relevant to not only the understanding of the basic processes of developmental morphogenesis and evolution of neurotransmitter pathways but is also of fundamental importance to a large class of laterality- and neurotransmitter-based birth defects. More than one in 8000 babies born to term exhibits errors of laterality and this work will lead to technologies to prevent, detect, and repair such teratologies. The work is currently being written up for publication.

We have received much support from the BRC. Last October, several members of my lab (myself, Wendy Zhang, Kelly Tseng, and Punita Koustubhan) visited MBL to use its unique facilities and staff for the above projects. In particular, we utilized a serotonin-specific electrode to detect extracellular serotonin in frog and chick embryos, and the biollistics station to transfect ion transporter DNA into regenerating tadpole blastemas. We look forward to continued collaborations with the BRC for our projects in embryonic patterning, regeneration, and stem cell biology.