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 A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

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

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>