Press Release

08.06.2015

New Insights into the Regeneration Process of the Zebrafish Brain

Scientists at Helmholtz Zentrum München (HMGU) have succeeded for the first time in directly observing stem cells in the brain of a vertebrate by means of live imaging. The observation of processes in the intact and injured brain led to an astonishing finding: Neurons are generated both by direct conversions of stem cells into postmitotic neurons and via intermediate progenitors amplifying the neuronal output. The study revealed changes in the behavior of stem cells underlying generation of additional neurons during regeneration, as the researchers reported in the journal Science.

Neural stem cells (green) in the Telencephalon of an adult Zebrafish. Source: HMGU

By means of live cell imaging, single stem cells were observed in intact and injured brains of adult zebrafish. The data show that adult neural stem cells (aNSCs) do not continually give rise to new neurons over a long period, as is often assumed, but do so only in a limited number. The direct conversion mode without cell division ultimately depletes the pool of aNSCs. This finding contradicts the current consensus of researchers that aNSCs give rise to many new neurons, which then later can be integrated as needed into the respective required function in the neuronal network.

In the intact brain, aNSCs rarely divide – and if so, they usually do it asymmetrically, i.e. by forming a typical, radial-shaped neural stem cell and a morphologically deviating neural progenitor cell. After an injury, such progenitors migrate to the injury site and divide symmetrically into two identical cells, thus increasing the number of neurons.

The live imaging showed that also in the injured brain, the aNSCs usually divide asymmetrically. “However, unlike in the intact brain, in the few symmetrical divisions no stem cells arise but rather two cells without the hallmarks of adult neural stem cells,” said Dr. Jovica Ninkovic, senior scientist at the Institute of Stem Cell Research, Helmholtz Zentrum München. “We assume that the cause for this new mode of cell division, which involves a loss of stem cells, is the brain injury,” he added. “In the intact brains we studied this does not occur.”

The study provides insights into the molecular behavior of aNSCs, which play a role in regeneration. “On this basis, the molecular mechanisms that change adult neural stem cell behavior following an injury shall be analyzed in further studies,” said Professor Magdalena Götz, director of the Institute of Stem Cell Research and head of the Department of Physiological Genomics at Ludwig Maximilians-Universität München. Studying these mechanisms in non-mammalian vertebrates may contribute to the understanding of the repair processes of neuronal damage in mammals, in which CNS regeneration is restricted. And if it were possible to elicit similar behavior in the injured human brain, this could also aid in its regeneration. 

Further information 

Original publication: Barbosa et al. (2015). Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain, Science, doi: 10.1126/science.aaa2729 

Link to publication: https://www.sciencemag.org/content/348/6236/789.short 

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The Institute of Stem Cell Research (ISF) investigates the basic molecular and cellular mechanisms of stem cell maintenance and differentiation. From that, the ISF then develops approaches in order to replace defect cell types, either by activating resting stem cells or by re-programming other existing cell types to repair themselves. The aim of these approaches is to stimulate the regrowth of damaged, pathologically changed or destroyed tissue.

Scientific Contact: 

Dr. Jovica Ninkovic, Helmholtz Zentrum München – Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Institut für Stammzellforschung Ingolstaedter Landstr. 1, 85764 Neuherberg - Tel.: + 49 89-3187-3756, E-mail: