Biography

2004 marked my 25th year carrying out research in the field of vertebrate limb formation. During that time I have utilized a number of experimental models including the regenerating salamander limb, the regenerating mouse digit, and the developing limbs of salamanders, frogs, chicks and mice. I have remained both productive and actively funded during this time. My studies have primarily focused on how cells communicate with one another to establish the 3-dimensional pattern of the adult limb. I have been lucky enough to be a participant in a field that has undergone an amazing transformation to become the best understood developing vertebrate organ, and to witness how our understanding of this organ has gained prominence in many aspects of applied science ranging from teratology to ecology.

The limb is formed by a series of interactions that occur between a specialized group of ectodermal cells at the tip of the limb bud that forms a structure called the apical ectodermal ridge (AER), and the mesenchymal cells that underlie the AER. The apical ectoderm produces factors that are necessary for distal outgrowth by the mesenchyme. Mesenchymal cells interact with one another and with the AER to establish spatially distinct patterns of gene expression followed by the differentiation of specific structures. The primary focus of my research is to understand how cells become distinct from one another. In the 1980's my cell lineage work on developing and regenerating amphibian limbs demonstrated similarities between development and regeneration, and also established the over-contribution of fibroblasts in the regeneration response. To begin to address regeneration in higher vertebrates, I pioneered in utero surgical techniques that make it possible to carry out regeneration studies on the developing mammalian limb. In the early 1990's I participated with Susan Bryant's lab in a study that demonstrated retinoic acid acted to induce a mesenchymal signaling center in the limb bud called the Zone of Polarizing Activity (ZPA). This finding has now been demonstrated with loss of function studies and with more sophisticated molecular probes with the same conclusion.

Ken Muneoka's Abstract