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Sonic hedgehog gene found in an unexpected place during limb development
Date:3/9/2010

riginally thought. Developmental biologists may have to rethink established theories about how limbs are patterned in vertebrates an effort that could provide insight into human birth defects.

"We used technology where a viral protein seeks out specific sequences of DNA," said Cortney M. Bouldin, a graduate student in the Interdisciplinary Program in Biomedical Sciences in the department of molecular genetics and microbiology. "We concentrated on disabling a protein essential for Sonic hedgehog signaling. Although it has been removed from the limb before, we wanted to specifically remove it from the ectoderm. When we did that, in the latter stages of development, we saw extra cartilage and the early beginnings of another digit."

Sonic hedgehog signaling in the ectoderm of limb buds may act as a buffering system that prevents unneeded growth, Bouldin said.

The UF research was sparked by studies of gene activity in the limb buds of mice by William J. Scott, D.V.M., Ph.D., a professor of pediatrics at the University of Cincinnati. Scott used a microarray experiment to examine gene expression levels in the ectoderm of mice limb buds, finding activity that could not be possible without the presence of Sonic hedgehog.

UF researchers were able to advance this investigation from cell studies to developing mice embryos by knocking out gene expression in a small region of the ectodermal layer. It allowed them to observe early limb development in the absence of Sonic hedgehog signaling.

"The view had been if you reduce signaling, if anything you would get fewer fingers," said Scott, who did not participate in the UF research. "We now know we can't disregard Sonic hedgehog signaling in the ectoderm. It still has its predominant effect in the tissue where it is made, but it does something more than we thought it did previously. When we try to understand problems that arise with limb growth in humans, we will be able to examine those
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Contact: John Pastor
jdpastor@ufl.edu
352-273-5815
University of Florida
Source:Eurekalert

Page: 1 2 3

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