Richard Kevin Hunt, Ph.D. - US grants

We propose to continue our studies on the surgical introduction of genetically marked embryonic cells into host organ anlagen in the clawed frog Xenopus laevis, and to track the clonal growth of marked cell progeny -- by direct observation of living chimeric tadpoles (where the marked cells are pigmented and the host organ is albino) and by computer reconstruction of internal tissues bearing cells marked with tetraploidy or nucleolar number. We will study the early divergence of tissue-specific lineages within the anlagen, and challenge the pigment cell lineages in a variety of ways -- e.g., testing their response to cell deaths in the surrounding host organ, the effects of developmental stage and of position within the organ, and how lineage patterns are preserved or altered in two classic preparations of developmental plasticity first identified by Ross Harrison some sixty years ago: pattern regulation -- in which mismatched fragments of an organ rudiment or a surgically disoriented whole rudiment 'adapt' to their new context and develop a normal organ pattern, and whole organ reconstitution from a single part of the organ rudiment. The long term aims of these studies are to define multicellular issues in organ development -- how layers form, how the organ grows and changes shape, how the right parts wind up in the right places -- in terms of the behaviors and ordinary cell traits of the cells whose clonal growth must both accomodate these multicellular patterns and also drive their formation. This basic research study has no immediate clinical applications to human disease, but should begin to provide a cellular characterization of organ development and growth necessary to understand human birth defects involving agenesis and undergrowth of body parts, as well as those involving derangement of organ structure.