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Events coordination during embryogenesis
Date:10/29/2013

A new study by Weill Cornell Medical College scientists reveals a mechanism through which the expression of genes is controlled a finding that highlights genetic mutations that can impair the timing of gene expression. Such mutations can affect the co-ordination of key events that are required for stepwise development of an organism, and can also give rise to cancer by turning on genes at the wrong time.

The study, published October 29 in the open access journal PLOS Biology, analyzes how the timing of gene expression is regulated in the notochord, the evolutionary and developmental precursor of the backbone. The notochord is the main feature that sets humans, mice, sea squirts and related animals (collectively known as chordates) apart from flies, worms and mollusks, and is essential for their development.

A crucial player in the development of the notochord is the Brachyury gene, which encodes a DNA-binding protein that switches on the expression of numerous notochord genes and ensures their sequential deployment during the formation of this pivotal structure. It was known that Brachyury directly binds distinct DNA sequences known as cis-regulatory modules (CRMs) that when bound act as molecular switches and control when and where these target notochord genes are expressed. What is addressed by this new study is how these switches could be flipped on by Brachyury at different times.

To clarify this point, scientists in the laboratories of Dr. Anna Di Gregorio and Dr. Yutaka Nibu, both in the Department of Cell and Developmental Biology, systematically analyzed the structure and activity of several notochord CRMs. The model they proposed suggests that some mutations don't appear to affect the ability of a CRM to be bound and activated but do affect the timing of expression of the gene containing the CRM. They found that in the sea squirt, timing of Brachyury switches depends on numbers: For genes that need to be turned
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Contact: PLOS Biology
biologypress@plos.org
Public Library of Science
Source:Eurekalert  

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