Holdener 96046530 The formation of specialized cells called mesoderm is a turning point during the embryonic development of species as diverse as jelly fish, insects, and mammals. Mesoderm organizes the early embryo, constitutes the vast majority of cells in the blood, heart, muscle, and bone of vertebrates, and indirectly influences the formation of all other major organ systems. Considerable progress has been made towards identifying growth factors with mesoderm inducing capabilities. However, even with these advances, we have a limited understanding of how these pathways are connected or how cells become competent to respond to these signaling molecules. One powerful approach toward defining the molecular mechanism of mesoderm differentiation is the analysis of mutants defective in this process. While a small number of mouse mutations have been identified that alter the characteristics of mesoderm, only the mouse msd mutation completely blocks mesoderm formation. Msd mutant embryos fail to form mesoderm and consequently do not form specialized tissues and organs. Extensive characterization of gene expression and cell differentiation demonstrate that defects in msd mutant embryos are restricted to mesoderm differentiation. Thus, the msd mutation defines a new gene critical for mesoderm differentiation and provides a valuable tool that can be utilized to identify additional components of this complex genetic pathway. The broad goal of Dr. Holdener's research is to understand the molecular mechanisms controlling mesoderm induction. To accomplish this goal, she proposes to characterize the chromosomal region encompassing the msd gene. These studies will include identification of delimiting deletion breakpoints, construction of a physical map of the region, and establishment of a DNA contig spanning the msd functional region. Combined, these studies will provide essential reagents for the future identification of the msd gene, a key component of the mammalian mesoderm induction pathway.
