Ed LauferDepartment of Genetics and Development, Columbia University, New York, NY, USA F1000 Faculty Member (since 13 February 2006)
Assistant Professor, Department of Genetics and Development, Columbia University Medical Center
PhD 1990, University of London
Postdoctoral Fellow 1991-1998, Harvard Medical School
Our lab studies pattern formation during vertebrate development, using the embryonic chick limb bud as our primary model system. We use a combination of surgical manipulations and molecular genetic approaches to explore how limbs develop.
Growth and patterning of the limb are coordinately controlled by multiple inductive signals that impinge on the developmentally plastic tissue of the early limb bud. These signals are produced by tightly regulated signaling centers, located at specific positions within the bud. We wish to understand what these signals are, how they exert their effects on the fate and arrangement of limb tissues, and how the signaling centers are themselves controlled. Two representative projects are described below.
The apical ectodermal ridge is one signaling center that is a specialized epithelial structure located at the tip of the limb bud. The ridge signals to the underlying mesenchyme through the production of fibroblast growth factors, FGFs, and promotes limb outgrowth and patterning. This process is complex and involves several interactive regulatory circuits between the ridge and the mesenchyme. Numerous genes expressed in the mesenchyme and implicated in these processes are regulated by ridge signals. These genes are expressed in overlapping domains that extend different distances from the ridge. Using a retrovirally mediated form of clonal analysis, we are investigating whether these genes are regulated directly by FGF signals, and if so, if there are distinct signaling thresholds that control their differential expression patterns.
While the signals produced by some signaling centers are known, many have not been molecularly identified. In another project, we are screening genes encoding novel secreted factors for expression patterns suggestive of important inductive functions. We have identified one gene that might regulate dorso-ventral limb pattern. Later in development it might also control developmentally significant apoptosis, such as that which leads to selective elimination of interdigital tissue. Experiments testing these possibilities through the analysis of mutant animals, as well as by gene misexpression are under way.
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