Shuo Lin Lab

Our long term goal is to understand vertebrate development at a genetic and molecular level and to develop zebrafish models for human genetic disorders. We are working to define the genetic pathways underlying hematopoiesis with a special interest in identifying those factors that mediate the initial determination and proliferation of hematopoietic stem cells. A saturation mutagensis screen, recently completed for zebrafish, allowed for the isolation of many mutants defective in blood formation. We have obtained these mutants and are analyzing them to identify those that many be defective in stem cell formation or proliferation. We have generated transgeneic fish that express green fluorescent protien as a reporter gene specifically in the hemapoietic progenitor cells. These fish make it possible to visualize the origin and migration of the earliest hematopoietic stem cells in a live embryo, and to purify them for in vitro studies. Using this system, coupled to genetic analysis of embryonic blood mutations, we have developed approaches that allow rapid detection of novel genes that are expressed in hematopoietic progenitor cells during embryogenesis. Given that the expression pattern and sequences of many hematopoietic genes are well conserved between fish, mice, and humans, our studies should ultimately lead to a better understanding of the molecular and genetic bases underlying mammalian hematopoietic development.