Uncovering the mechanisms that govern morphogenesis, the generation of biological form

For a tissue or organ to achieve correct shape and size, cellular differentiation and growth must be coordinately regulated. My current favored model system for the study of morphogenetic processes is the developing skeleton, in particular the chick forelimb or wing (I also have a strong interest in kidney development).

Although most bones are generated from a common progenitor cell type, each forming element acquires a unique shape. This is true even for paired structures, such as the limbs, in which bones from one side are mirror images of those on the other. Alterations in skeletal structure are components of many birth defects, but also are important for generating morphological diversity throughout evolutionary history. Surprisingly, studies in the mouse suggest that many deviations in skeletal development result from the effect of a genetic lesion on the formation or regulation of the early prechondrogenic condensate, the precursor to the cartilage element. For this reason, I am interested in determining how condensates are formed and the mechanisms that control their size and shape.

Some of the initial questions we will address are:
1. What is the process by which limb mesenchyme cells become prechondrocytes and how is condensation of the progenitors initiated?

2. What role does cell adhesion play in forming and regulating the shape of developing cartilage elements? Is cell adhesion a major factor in keeping adjacent elements from fusing?

3. What is the basis of the differential response to specific signals of cells that form the proximal (near the body) and distal (digits) limb elements?

To address these issues, we rely on a combination of classical embryological techniques (e.g. embryo surgery and tissue explant cultures), genetics (mouse), genomics (DNA microarrays) and biochemistry.

Dudley, A. T., Godin, R. E. and Robertson, E. J. (1999) Interaction between FGF and BMP signaling pathways regulates development of metanephric mesenchyme. Genes & Dev. 13: 1601-1613.

Godin, R. E., Robertson, E. J. and Dudley, A. T. (1999) Role of BMP family members during kidney development. Int. J. Dev. Biol. 43: 405-411.

Dudley, A. T., Ros, M. A. and Tabin, C. J. (2002) A re-examination of proximodistal patterning during vertebrate limb development. Nature 418: 539-544.

Oxburgh L, Dudley AT, Godin RE, Koonce CH, Islam A, Anderson DC, Bikoff EK, Robertson EJ. BMP4 substitutes for loss of BMP7 during kidney development. Dev Biol. 2005 Oct 15;286(2):637-46. Epub 2005 Sep 8.

Dudley AT, Tabin CJ. Deconstructing phosphatases in limb development. Nat Cell Biol. 2003 Jun;5(6):499-501. No abstract available.

View all publications by publications by Andrew T. Dudley listed in the National Library of Medicine (PubMed).