Forum für Wissenschaft, Industrie und Wirtschaft

Hauptsponsoren:     3M 
Datenbankrecherche:

 

How Do Cells Tell Time? Scientists Develop Single-Cell Imaging to Watch the Cell Clock

14.11.2012
A new way to visualize single-cell activity in living zebrafish embryos has allowed scientists to clarify how cells line up in the right place at the right time to receive signals about the next phase of their life.

Scientists developed the imaging tool in single living cells by fusing a protein defining the cells’ cyclical behavior to a yellow fluorescent protein that allows for visualization.

Zebrafish embryos are already transparent, but with this closer microscopic look at the earliest stages of life, the researchers have answered two long-standing questions about how cells cooperate to form embryonic segments that later become muscle and vertebrae.

Though these scientists are looking at the molecular “clock” that defines the timing of embryonic segmentation, the findings increase understanding of cyclical behaviors in all types of cells at many developmental stages – including problem cells that cause cancer and other diseases. Understanding how to manipulate these clocks or the signals that control them could lead to new ways to treat certain human conditions, researchers say.

Embryonic cells go through oscillating cycles of high and low signal reception in the process of making segmented tissue, and gene activation by the groups of cells must remain synchronized for the segments to form properly. One of a handful of powerful messaging systems in all vertebrates is called the Notch signaling pathway, and its precise role in this oscillation and synchronization has been a mystery until now.

In this study, the researchers confirmed that the cells must receive the Notch signal to maintain synchronization with nearby cells and form segments that will become tissue, but the cells can activate their genes in oscillating patterns with or without the signal.

“For the first time, this nails it,” said Sharon Amacher, professor of molecular genetics at Ohio State University and lead author of the study. “This provides the data that cells with disabled Notch signaling can oscillate just fine, but what they can’t do is synchronize with their neighbors.”

The imaging also allowed Amacher and colleagues to determine that cell division, called mitosis, is not a random event as was once believed. Instead, division tends to occur when neighboring cells are at a low point of gene activation for signal reception – suggesting mitosis is not as “noisy,” or potentially disruptive, as it was previously assumed.

The study is published in the November issue of the journal Developmental Cell.

Amacher’s work focuses on the creation of these tissue segments, called somites, in the mesoderm of zebrafish embryos – this region gives rise to the ribs, vertebrae and muscle in all vertebrates, including humans.

“This early process of segmentation is really important for patterning a lot of subsequent developmental events – the patterning of the nervous system and the vasculature, much of that depends on this clock ensuring that early development happens properly,” Amacher said.

Unlike the well-known 24-hour Circadian clock, however, the activities of cells at the earliest stages of development can occur within a matter of minutes – which makes their clocks very challenging to study.

This research was aided by collaboration among biologists and physicists, including development of a powerful MATLAB-based computational analysis by co-author Paul François, assistant professor of physics at McGill University. François helped to semi-automate cell tracking, as well as to convert raw data about each cell’s phase into maps enabling more specific visualizations. He worked with Emilie Delaune, a postdoctoral fellow who constructed the imaging tool and had previously tracked cells by hand, and graduate student Nathan Shih. Amacher, Delaune and Shih conducted the research while at the University of California, Berkeley. Amacher joined the Ohio State faculty in July.

Experts in tissue segmentation liken the oscillating cycle of gene activation and de-activation that cells go through before they form somites to the wave that fans perform in a stadium. According to the segmentation clock, genes are turned on, proteins are made, proteins then inhibit gene activation, and so on, and the pattern repeats until all necessary somites are formed. Neighbor cells must be in sync with each other just as sports fans in the same section must stand and sit at the same time to effectively form a wave.

Zebrafish somites form every 30 minutes, meaning that during any one cycle of the wave, a cell is engaged in making protein for only about five minutes. To generate the imaging tool, researchers linked a yellow fluorescent protein to a cyclic protein known to have a short lifespan. The resulting short-lived fluorescent fusion protein allowed Amacher and colleagues to look at single cells along with their neighbors to observe how they stayed synchronized as they did the wave.

Researchers in this field had previously thought that the Notch signaling pathway may be needed to start the clock in these cyclic genes, though conflicting data had shown that the clock could run without the signal.

Amacher’s imaging showed that, indeed, Notch was required only to maintain synchronization, but not to start the oscillating clock. She and colleagues tested this idea by combining the imaging tool with three mutant cell types with disabled Notch signals. Cells in all three mutants could oscillate, but not in a synchronized fashion, explaining how they failed to form segments in the way that cells receiving the Notch signal could.

Defects in Notch signaling are associated with human congenital developmental disorders characterized by malformed ribs and vertebrae, suggesting this work offers insight into potential therapies to prevent these defects.

The researchers next sought to determine whether cell division interrupted the synchrony needed for creation of the segments. Mitosis, occurring among 10 to 15 percent of embryonic cells at any one time, is considered a source of biological “noise” because when cells divide, they stop activating genes. If division were happening randomly, as previously thought, instead of in a pattern, the very cell division needed for organism growth could also disrupt clock synchrony, creating problems that segmenting organisms would have to overcome.

The study showed, however, that most cells divided when their neighbors were at a low point of gene activation – at the bottom of a wave – suggesting that cell division doesn’t occur at random. The study team noted that the two daughter cells created from a fresh division are more tightly synchronized with each other than are any other cell neighbors in the area.

Under normal conditions, these two daughters resynchronize with their neighbors in short order. In embryos lacking Notch signaling, newly divided daughters appeared as a pair of tightly synchronous cells in a largely asynchronous sea, showing that oscillation could resume without the signaling pathway. Without Notch, the daughter cells gradually drifted out of synchrony, becoming like their asynchronous neighbors.

Amacher said these findings could be incorporated into models of developmental cell behavior to further advance cell biology research.

“Most of our tissues and organs are not made up of the same types of cells. They have different jobs. So you don’t want them to respond identically to every signal; you want them to have different responses,” she said. “We need to understand systems like this that help cells not only interpret the signals in their environment, but do the right thing when they get that signal.”

This work was funded by the National Institutes of Health, Association Française contre les Myopathies, a Marie-Curie Outgoing International Fellowship, a Pew Scholar Award, the Natural Science and Engineering Research Council of Canada Discovery Grant program and Regroupement Québécois pour les matériaux de pointe.

Contact: Sharon Amacher, (614) 292-8084; Amacher.6@osu.edu
Written by Emily Caldwell, (614) 292-8310; Caldwell.151@osu.edu

Emily Caldwell | Newswise Science News
Further information:
http://www.osu.edu

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unterwasserroboter soll nach einem Jahr in der arktischen Tiefsee auftauchen

Am Dienstag, den 22. August wird das Forschungsschiff Polarstern im norwegischen Tromsø zu einer besonderen Expedition in die Arktis starten: Der autonome Unterwasserroboter TRAMPER soll nach einem Jahr Einsatzzeit am arktischen Tiefseeboden auftauchen. Dieses Gerät und weitere robotische Systeme, die Tiefsee- und Weltraumforscher im Rahmen der Helmholtz-Allianz ROBEX gemeinsam entwickelt haben, werden nun knapp drei Wochen lang unter Realbedingungen getestet. ROBEX hat das Ziel, neue Technologien für die Erkundung schwer erreichbarer Gebiete mit extremen Umweltbedingungen zu entwickeln.

„Auftauchen wird der TRAMPER“, sagt Dr. Frank Wenzhöfer vom Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI) selbstbewusst. Der...

Im Focus: Mit Barcodes der Zellentwicklung auf der Spur

Darüber, wie sich Blutzellen entwickeln, existieren verschiedene Auffassungen – sie basieren jedoch fast ausschließlich auf Experimenten, die lediglich Momentaufnahmen widerspiegeln. Wissenschaftler des Deutschen Krebsforschungszentrums stellen nun im Fachjournal Nature eine neue Technik vor, mit der sich das Geschehen dynamisch erfassen lässt: Mithilfe eines „Zufallsgenerators“ versehen sie Blutstammzellen mit genetischen Barcodes und können so verfolgen, welche Zelltypen aus der Stammzelle hervorgehen. Diese Technik erlaubt künftig völlig neue Einblicke in die Entwicklung unterschiedlicher Gewebe sowie in die Krebsentstehung.

Wie entsteht die Vielzahl verschiedener Zelltypen im Blut? Diese Frage beschäftigt Wissenschaftler schon lange. Nach der klassischen Vorstellung fächern sich...

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Forscher entwickeln maisförmigen Arzneimittel-Transporter zum Inhalieren

Er sieht aus wie ein Maiskolben, ist winzig wie ein Bakterium und kann einen Wirkstoff direkt in die Lungenzellen liefern: Das zylinderförmige Vehikel für Arzneistoffe, das Pharmazeuten der Universität des Saarlandes entwickelt haben, kann inhaliert werden. Professor Marc Schneider und sein Team machen sich dabei die körpereigene Abwehr zunutze: Makrophagen, die Fresszellen des Immunsystems, fressen den gesundheitlich unbedenklichen „Nano-Mais“ und setzen dabei den in ihm enthaltenen Wirkstoff frei. Bei ihrer Forschung arbeiteten die Pharmazeuten mit Forschern der Medizinischen Fakultät der Saar-Uni, des Leibniz-Instituts für Neue Materialien und der Universität Marburg zusammen Ihre Forschungsergebnisse veröffentlichten die Wissenschaftler in der Fachzeitschrift Advanced Healthcare Materials. DOI: 10.1002/adhm.201700478

Ein Medikament wirkt nur, wenn es dort ankommt, wo es wirken soll. Wird ein Mittel inhaliert, muss der Wirkstoff in der Lunge zuerst die Hindernisse...

Im Focus: Exotische Quantenzustände: Physiker erzeugen erstmals optische „Töpfe" für ein Super-Photon

Physikern der Universität Bonn ist es gelungen, optische Mulden und komplexere Muster zu erzeugen, in die das Licht eines Bose-Einstein-Kondensates fließt. Die Herstellung solch sehr verlustarmer Strukturen für Licht ist eine Voraussetzung für komplexe Schaltkreise für Licht, beispielsweise für die Quanteninformationsverarbeitung einer neuen Computergeneration. Die Wissenschaftler stellen nun ihre Ergebnisse im Fachjournal „Nature Photonics“ vor.

Lichtteilchen (Photonen) kommen als winzige, unteilbare Portionen vor. Viele Tausend dieser Licht-Portionen lassen sich zu einem einzigen Super-Photon...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

IHR
JOB & KARRIERE
SERVICE
im innovations-report
in Kooperation mit academics
Veranstaltungen

European Conference on Eye Movements: Internationale Tagung an der Bergischen Universität Wuppertal

18.08.2017 | Veranstaltungen

Einblicke ins menschliche Denken

17.08.2017 | Veranstaltungen

Eröffnung der INC.worX-Erlebniswelt während der Technologie- und Innovationsmanagement-Tagung 2017

16.08.2017 | Veranstaltungen

 
VideoLinks
B2B-VideoLinks
Weitere VideoLinks >>>
Aktuelle Beiträge

Eine Karte der Zellkraftwerke

18.08.2017 | Biowissenschaften Chemie

Chronische Infektionen aushebeln: Ein neuer Wirkstoff auf dem Weg in die Entwicklung

18.08.2017 | Biowissenschaften Chemie

Computer mit Köpfchen

18.08.2017 | Informationstechnologie