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 Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>