Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Solving the puzzle of stem cell division

06.10.2008
The central question of developmental biology is how a single fertilized egg can divide repeatedly to produce multiple different cell types. An article in this week's issue of the scientific journal Cell from Jürgen Knoblich's group at the Institute of Molecular Biotechnology (IMBA) in Vienna, Austria sheds fresh light on this key issue.

It had previously been established that asymmetric cell division is extremely important in determining cell fates. Asymmetric cell division occurs when a molecule is inherited by only one of the two cells that arise following cell division (mitosis).

It was established well over a decade ago that in the sensory organ precursor cells (SOP cells) of the fruit fly Drosophila melanogaster the "Numb" protein is segregated into only one of the two daughter cells. How this takes place, however, has remained a matter of conjecture despite the intense efforts of at least 10 groups worldwide.

Knoblich was one of the scientists involved in the early characterization of the molecules involved in Numb's asymmetric localization and he has continued to study the mechanism from his early post-doc days to the present. Some time ago he and others showed that the protein "Lethal giant larvae" (Lgl) and an atypical protein kinase C (aPKC) were involved but scientists were unable to say how the phosphorylation of Lgl by aPKC affected Numb's localization.

The facilities at the IMBA and the adjoining Institute for Molecular Pathology (IMP) have enabled a wide range of methods to be brought to bear on the problem. Key to Knoblich's work has been a recently developed method for imaging live flies. Knoblich has been studying Numb localization by means of a uniquely multidisciplinary approach, combining live imaging methods with genetics and biochemistry. The kinase AuroraA (Aur-A) was known to be activated at the start of cell division and to be required for Numb activity. Knoblich has now shown that AurA phosphorylates a protein known as Par-6, causing actication of aPKC and thus the phosphoylation of Lgl and its dissociation from the Par complex. When Lgl is no longer bound to the Par complex, a further protein, known as "Bazooka", may bind in its place. AurA activation thus effects a remodelling of the Par complex. As Knoblich further showed, the Par complex can only phosphorylate the Numb protein when Bazooka is present in the complex. Phosphorylated Numb is released from the cortex and because it diffuses only slowly through the cell it is restricted to a crescent on the opposite side.

Knoblich's results have identified a cascade of interactions among the various proteins required for restricting Numb's localization to a cortical crescent on the opposite side of the cell. A similar process was shown to operate in cultured human cells, so it is likely that the molecular mechanism responsible for regulating asymmetric cell division in Drosophila neuroblasts may control self-renewal and prevent tumour formation in other types of stem cell. The present findings are thus likely to have important ramifications in tumour biology. Indeed, mutations in the numb gene have been shown to cause uncontrolled growth of neuroblasts, leading to the formation of brain tumours and a similar phenotype results from expression of a constitutively active form of a PKC. Knoblich now reports that in this latter case the tumourigenic activity is completely removed by overexpressing Numb. The human Numb analogue is known to act as a suppressor of breast cancer, whereas the Lgl homologue has been implicated in metastasis of colon carcinomas (tumours are more aggressive in the absence of Lgl). The potential implications of Knoblich's latest results for human therapy are obvious, although Knoblich stresses that they lie well in the future.

Publication: Frederik Wirtz-Peitz, Takashi Nishimura, and Juergen A. Knoblich: Linking Cell Cycle to Asymmetric Division: Aurora A Phosphorylates the Par Complex to Regulate Numb Localization. Cell, October 3, 2008

F.W.P. was supported by a Ph.D. fellowship of the Boehringer Ingelheim Fonds; T.N. is supported by a long-term fellowship of the HFSP; work in J.A.K.'s lab is supported by the Austrian Academy of Sciences, FWF, WWTF, EU EUROSYSTEMS, and ONCASYM.

Contact:
Dr. Heidemarie Hurtl, IMBA Communications
Tel. +43 1 79730-3625
Mobile: +43 (0)664 8247910
heidemarie.hurtl@imba.oeaw.ac.at
Scientific Contact:
Dr. Jürgen Knoblich
juergen.knoblich@imba.oeaw.ac.at

Dr. Heidemarie Hurtl | idw
Further information:
http://www.imba.oeaw.ac.at/research/juergen-knoblich/

More articles from Life Sciences:

nachricht Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Purdue cancer identity technology makes it easier to find a tumor's 'address'

16.11.2018 | Health and Medicine

Good preparation is half the digestion

16.11.2018 | Life Sciences

Microscope measures muscle weakness

16.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>