Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A "Repulsive" Protein Guides Blood Vessel Development

19.11.2004


In a developing embryo, the growth of nerves cannot outpace the establishment of life-giving blood vessels. Now, researchers have found that a protein intimately involved in blood vessel patterning actually belongs to a family of proteins known to guide neural development.



The researchers said the studies provide more evidence of communication between developing nerves and blood vessels. Understanding how those networks talk to each other could help researchers devise methods to prevent blood vessel growth in tumors selectively - an approach to cancer treatment known as anti-angiogenesis. The research team, which included Howard Hughes Medical Institute investigators David D. Ginty and Thomas M. Jessell, published its findings November 18, 2004, in Science Express, the early online version of the journal Science. Co-first authors of the paper were Chenghua Gu in Ginty’s laboratory at The Johns Hopkins University School of Medicine, and Yutaka Yoshida in Jessell’s laboratory at Columbia University.

In their experiments, the researchers explored the roles of two proteins involved in vascular development. One of the molecules, Semaphorin 3E (Sema3E), is a member of a family of protein signals that guides the growth of nerve cells. The other protein, plexin-D1, is a receptor protein that nestles in the membranes of growing cells and responds to external signaling proteins. Ginty said that before the current study, plexin-D1 was known to be important for vascular development, but the specific signal to which it responded was a mystery. The molecule was also considered an important receptor in nerve cell development, and for that reason Jessell’s laboratory was actively investigating plexin-D1.


Studies by Ginty and others, including former HHMI investigator Marc Tessier-Lavigne, who is now at Genentech, had shown that some of the semaphorins bind to a receptor called neuropilin, which is critical for vascular patterning in the embryo. However, in their earlier work, Gu, Ginty, and co-author Alex Kolodkin showed that semaphorins do not need to bind to neuropilin for normal patterning to occur. “That work set us looking for other potential mechanisms by which semaphorins might control vascular pattern development,” said Ginty. The researchers found Sema3E in regions of the developing embryo that suggested that it should have a role in the patterning of blood vessels. They also found a strikingly similar pattern of expression of the blood vessel cell receptor plexin-D1, leading the researchers to hypothesize that Sema3E might be the signaling molecule that interacts with plexin-D1. If this were true, it suggested that Sema3E exerts a “repulsive” force, channeling the blood vessels to grow along their proper course. Meanwhile, Yoshida discovered that unlike other members of the same protein family, Sema3E binds selectively to plexin-D1 - a strong hint that the two signals work together to control vascular patterning. Yoshida also found that Sema3E can bind to plexin-D1 whether or not it binds to neuropilin.

Researchers noted that in contrast to the careful patterning of blood vessels in normal mice, the pattern of blood vessels in mice lacking plexin-D1, produced in Jessell’s laboratory, was haphazard. Furthermore, knockout mice lacking Sema3E, produced in the laboratory of co-author Christopher Henderson of the Developmental Biology Institute in France, showed the same defective patterning. In additional experiments, Gu showed that overexpression of Sema3E protein in specific regions of chick embryos prevented vascular growth into those areas. “Sema3E is a very potent chemorepellent for developing blood vessels,” Ginty noted. “So, one possibility is that drugs that mimic this function could be useful in preventing growth of the new blood vessels required by tumors.” “One of the really interesting things about this paper is that it questions the idea that Sema3E’s binding to neuropilin is required for vascular patterning,” said Jessell. “This, together with the finding that Sema3E interacts with plexin-D1, independent of neuropilin, may turn some of the preconceptions about the role of neuropilins in vascular patterning on their head.”

Jessell and his colleagues are now exploring whether Sema3E and plexin-D1 also contribute to the development of connections in the spinal cord. Ginty and his colleagues plan to explore the role of the proteins in neural development, as well as whether the combination is involved in vascular patterning in the limbs.

Jim Keeley | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>