Mechanism To Organize Nervous System Conserved In Evolution

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Mechanism To Organize Nervous System Conserved In Evolution

http://www.medicalnewstoday.com/medicalnews.php?newsid=51642

A study led by University of California, San Diego biologists

suggests that, contrary to the prevailing view, the process in early

development that partitions the nervous system in fruit flies and

vertebrates, like humans, evolved from a common ancestor.

In the September 12 issue of the journal Public Library of Science

Biology, the researchers report that in both fruit fly and chick

embryos proteins called BMPs play similar roles in telling cells in

the early embryo to switch certain genes on and off, specifying the

identity of the cells making up the three primary subdivisions of the

central nervous system. The findings suggest a unified model of early

neural development in which at least part of the mechanism for

creating neural patterning has been preserved from a shared ancestral

organism that lived over 500 million years ago.

" We have provided the first evidence for a common role of BMPs in

establishing the pattern of gene expression along the dorsal-ventral

axis of the nervous system of vertebrates and invertebrates, " said

Ethan Bier, a professor of biology at UCSD and senior author on the

study. " Our results suggest that this process has been conserved from

a common ancestor rather than evolving separately as had been

previously believed. "

Early in the development of a complex organism, when it is a ball of

indistinguishable cells, BMP gradients are responsible for

partitioning embryos into neural and non-neural tissue. During this

phase, often referred to as neural induction, high levels of BMPs in

non-neural regions actively suppress neural development. This role of

BMPs is one of the best examples of a conserved evolutionary process.

However, it has been less clear whether BMPs also play a common role

in further subdividing the nerve tissue into three distinct regions.

Although the so-called neural identity genes get switched on in a

similar pattern in relation to the BMP source, it has been speculated

that distinct mechanisms operate to determine those activation

patterns in fruit flies versus vertebrates. For example, in

vertebrates a protein called Hedgehog is a key patterning agent in

this process, while in flies a gradient of a different protein called

Dorsal plays a comparable role.

" Because of the dominant role of the gradient of Dorsal protein, it

has not been possible to directly test the role of BMPs in patterning

nerve tissue in fruit flies. " explained Mieko Mizutani, a

postdoctoral researcher in biology at UCSD and the lead author on the

paper. " Eliminating Dorsal results in embryos that do not have any

nerve tissue. Therefore, we had to genetically reconstruct embryos

that had a uniform concentration of Dorsal throughout. Then we could

examine how neural patterning was affected by a BMP gradient. The

techniques took approximately fours years to develop and will also be

useful for future research to understand how the many genes of the

genome are turned on or off in groups. "

In these embryos with a uniform concentration of Dorsal, the

researchers switched on the gene for the fruit fly BMP in a narrow

stripe. Using a technique called multiplex labeling that Bier,

Mizutani and fellow UCSD biologists developed two years ago, Mizutani

was able to use different colored fluorescent molecules to determine

which neural identity genes were activated in response to the BMP

gradient. She determined that BMPs acted the same way as they do

earlier during neural induction, namely to shut off neural identity

genes. Because BMPs can shut some neural genes off better than

others, the pattern in which the neural identity genes get switched

off depends on the concentration of BMP.

The finding that a BMP gradient controlled neural development in

fruit flies prompted the authors to ask whether the same might be

true in vertebrates. Bier and Mizutani collaborated with Henk

Roelink, a professor of biology at the University of Washington,

Seattle and his graduate student Néva Meyer. They performed

analogous experiments on chick embryos.

Roelink and Meyer added doses of BMP to a Petri plate containing

nerve tissue from early chick embryos. As with fruit flies, they had

to hold constant the concentration of another protein involved in

dorsal-ventral patterning (in this case Hedgehog rather than Dorsal).

The neural identity genes in chick responded to the BMP gradient just

as their counterparts responded in fruit flies. " Our findings suggest

that BMPs may once have been sufficient to organize the entire dorsal-

ventral axis of a common ancestor, " concluded Bier.

" BMPs and the neural identity genes appear to have been conserved in

evolution, while other cues such as Dorsal in flies and Hedgehog in

vertebrates may have been borrowed from other pattern systems after

the split between vertebrate and invertebrate lineages. As larger

organisms evolved, the gradient of a single protein may not have been

able to provide sufficient information to subdivide the embryo from

top to bottom. "