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The battle of the morphogens: How to get ahead in the nervous system
Date:9/1/2011

If you think today's political rhetoric is overheated, imagine what goes on inside a vertebrate embryo. There, two armies whose agendas are poles apart, engage in a battle with consequences much more dire than whether the economy will recover---- they are battling for whether you (or frogs or chickens) will have a forebrain.

In a study published in the August 19 online edition of Genes & Development, Salk Institute investigators led by Greg Lemke, Ph.D., professor in the Molecular Neurobiology Laboratory, reveals that a foot soldier of one army---- the ventralizers---deploys a weapon that disarms the other---- the dorsalizers---leaving the embryo free to develop a proper brain. Those findings define how the embryonic nervous system develops and could shed light on mechanisms underlying colon cancer.

The Lemke lab has a long-term interest in how different cell types emerging along the dorsal/ventral, or "top-to-bottom", axis of the nervous system are determined by competition between two secreted factors, or "morphogens"----the dorsalizer Wnt, trickling down from the brain or eye's "north pole" and its ventralizing opponent Sonic Hedgehog, creeping up from the "south".

"Opposing morphogen gradients regulate genes that must be expressed at either the top or the bottom of the brain for normal development to occur," says Lemke. "Those same signals must also be carefully controlled later on in mature tissues. An important example is provided by cancer, where over-active Wnt signaling is often linked to tumor formation."

The Lemke lab previously showed that a pair of Vax proteins, which bind DNA and regulate gene expression, are expressed in a gradient opposite to Wnts----high at the brain or eye's south, or ventral, pole and lower as you move north. This led them to propose that in response to Sonic Hedgehog signaling, Vax proteins ventralize tissues by blocking Wnt signals.

To test this idea they set up a genom
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Contact: Andy Hoang
Ahoang@salk.edu
619-861-5811
Salk Institute
Source:Eurekalert  

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