Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Morphogenesis through Flowing Tissue

24.02.2015

Heidelberg researchers transform classical understanding through in vivo analysis of eye development

In an in vivo analysis of eye development, researchers at Heidelberg University and the University of Freiburg have gained fundamental new insight into the development of coloboma of the eye, prompting them to revise the classical view of the development of this sensory organ in vertebrates.


The figure shows two stages of eye development, the optic vesicle (top) and the optic cup (below).

Heidelberg Centre for Organismal Studies (COS)

The team led by developmental and cell biologists Dr. Stephan Heermann and Prof. Dr. Jochen Wittbrodt of the Heidelberg Centre for Organismal Studies (COS) used in vivo 4D microscopy to demonstrate that directed tissue flow transforms the optic vesicle into the optic cup during eye development.

This is not only critical for understanding the cause of coloboma (“cat eye syndrome”), but also means that eye development in vertebrates, including humans, is fundamentally different than has been taught for more than 70 years. The results of their research were published the journal eLife.

In their analysis, the research group, which included Prof. Dr. Kerstin Krieglstein of the Department of Molecular Embryology at the Institute of Anatomy and Cell Biology of the University of Freiburg, combined modern genetics with time-lapse microscopy of living cells. This allowed them to record the dynamics of organ morphogenesis. They made three fundamental discoveries in the process.

“We now know that that an organ forms through flow, not incrementally in steps. If the flow is stopped, coloboma develops. And we found the source of the stem cells in the eye, which is of major importance in stem cell research,” explains Prof. Wittbrodt.

The eye is an outgrowth of the brain and forms in the embryo from a sac-like vesicle that quickly transforms into an optic cup with an interior retina surrounded on the outside by pigment epithelium. Major problems result if this step fails; the optic cup does not close and results in a coloboma, one of the most frequent causes of paediatric blindness.

Until now, the optic cup was believed to develop rather statically from two layers of the vesicle, with the lens-facing layer becoming the retina and the other, lens-averted layer forming the pigmented epithelium. “However in the detailed investigation of this developmental step using high-resolution video microscopy on living fish, we discovered that the optic cup forms from a dynamic flow of lens-averted cells into the lens-facing optic cup, exactly the opposite of static development,” explains Dr. Heermann.

The researchers also found the growth factor that controlled the flow of tissue and was thus essential for eye development. The signalling pathway of the growth factor BMP must be modulated for the tissue to flow and transform the vesicle into the cup. “Without this modulation, the tissue remains stuck on the lens-averted side and begins to develop into the retina,” continues Stephan Heermann.

Yet another important finding of the study is the close connection of movement (morphogenesis) and differentiation. It was already known that precursor cells begin to differentiate into nerve cells of the retina in the centre of the interior optic cup and continuously advance into the periphery. “The new data gives us a completely new perspective on this event,” explains Jochen Wittbrodt.

The cells that differentiate first are already located in the interior of optic cup at the start of development. The cells that differentiate later do not flow into the optic cup until later, and only there they are initially subject to the influence of differentiation signals. Due to their position, these cells are not exposed to the signals in the early phase. This is especially true in the stem cells of the fish model system studied.

“Using 4D microscopy, we were now able to identify and analyse this special population of cells,” explains Jochen Wittbrodt. It was clear that there are two distinct areas in the lens-averted domain of the developing optic cup, which is where these future stem cells are initially located. These cells are the last to reach the optic cup and end up at the boundary between the retina and the pigment epithelium. “Our findings describe the origin of the stem cells in the eyes of fish for the first time and imply that these cells are defined early. At first glance this may not seem very interesting for humans, who no longer have stem cells in the eye. But this data is extremely important for stem cell research.”

According to Stephan Heermann, the current results have high biomedical significance because they explain the origin of a coloboma. The bifurcated flow of tissue described creates a fissure on the underside of the eye, the optic fissure. As the eye continues to develop, it is critical that this fissure close so the eye can see in all directions. “The current data clearly indicates that both the development of the optic fissure and its closure essentially depend on the coordinated flow of tissue.” A coloboma is the medical term for an open optic fissure.

Original publication:
S. Heermann, L. Schütz, S. Lemke, K. Krieglstein, J. Wittbrodt: Eye morphogenesis driven by epithelial flow into the optic cup facilitated by modulation of bone morphogenetic protein. eLIFE, February 24, 2015, doi: 10.7554/eLife.05216

Internet information:
Publication: http://dx.doi.org/10.7554/eLife.05216
Films on eye development:
http://youtu.be/IGjjRGHDYJE / http://youtu.be/Q6aMe9J6o8Q / http://youtu.be</g4HNk9NzajU

Contact:
PD Dr. Stephan Heermann, Prof. Dr. J. Wittbrodt
Centre for Organismal Studies
Phone: +49 6221 54-8687 (Heermann), -6499 (Wittbrodt)
stephan.heermann@cos.uni-heidelberg.de, jochen.wittbrodt@cos.uni-heidelberg.de

Communications and Marketing
Press Office
Phone: +49 6221 54-2311
presse@rektorat.uni-heidelberg.de

Marietta Fuhrmann-Koch | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>