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The mother lode of mutations

Philadelphia, PA -- After five years and thousands of zebrafish breeding experiments, Mary C. Mullins, PhD, associate professor of cell and developmental biology at the University of Pennsylvania School of Medicine and colleagues have published a description of dozens of mutations that will help determine the earliest steps in vertebrate development, which take the spherical embryo to a complex creature. These discoveries are described in a pair of papers in the June Developmental Cell and are featured on the cover of that issue. In time, these discoveries may help researchers understand human sterility and fertility problems, as well as what causes certain birth defects.

Molecular control of the step-by-step process of how the zebrafish body unfolds relies to some extent on maternally driven processes. These depend on proteins derived only from the egg, which are critical to embryonic development prior to the activation of the new embryo's own genome. In vertebrates, maternal gene products direct such essential processes as fertilization; the first cellular divisions of the embryo; and the head-to-tail arrangement of developing cells. The genes also control morphogenetic movement, the migration of cells to form the three-dimensional structure of the embryo.

In 1998 the Mullins lab embarked on a large-scale maternal-effect mutant screen, not previously performed in a vertebrate animal model. In addition to the 68 maternal mutations, through inbreeding studies, they also discovered five paternally derived mutations. Daniel S. Wagner, PhD, and Roland Dosch, PhD, both postdoctoral fellows in the Mullins lab, spent five-plus years each on this intensive research project.

"These maternal processes are well-studied in invertebrates, but not vertebrates," says Mullins. "Genetic screens have been extremely powerful in identifying key genes and understanding the processes involved." This collection of mutants p
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
23-Jun-2004


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