Researchers from the RIKEN Center for Developmental Biology, Kobe, have shown that neurons called Purkinje cells can not only be generated from embryonic stem (ES) cells, but can also become fully integrated into existing neuronal circuits when transplanted into the brains of mouse fetuses1.
Purkinje cells are the largest neuronal subtype in the mammalian brain, and their output in the brain region called the cerebellum controls balance, co-ordination and movement.
Yoshiki Sasai and his colleagues cultured ES cells and then treated them at different times with the hormone insulin, the naturally occurring chemical cyclopamine, and a protein called fibroblast growth factor 2, which normally induces the differentiation of Purkinje cells at a specific location in the developing hindbrain.
This treatment caused the ES cells to express genes that are specific for Purkinje cells, and then to differentiate into mature neurons with the extensive, two-dimensional dendritic tree and electrical properties that are characteristic of Purkinje cells. They found that the differentiation of the cells recapitulate the events that take place during neural development. The Purkinje cell-specific genes were expressed in the same sequence as in the embryo, and the immature cells exited the cell cycle, or stopped dividing, on a timescale comparable to that of the neurons in the developing cerebellum.
Sasai and colleagues then separated immature Purkinje cells from the ES cell cultures, and transplanted them into the brains of embryonic mice, injecting approximately 10,000 cells into each animal. They found that the transplanted cells integrated effectively into their proper location within the circuitry of the cerebellum. The majority began to express Purkinje cell genes between 1 to 4 weeks after transplantation, and then differentiated into mature neurons, each with a long axon projecting down into the deep cerebellar nuclei.
The methods of Sasai and his team significantly improve on earlier methods for generating Purkinje cells from ES cell cultures. By successfully reproducing the microenvironment of the developing cerebellum, they generated up to 30-fold more Purkinje cells than previous methods.
These results therefore raise the possibility of developing cell transplantation therapies the cerebellar ataxias, a group of movement disorders characterized by severe motor in-coordination, which occur because of Purkinje cell degeneration.
“As a next step, we are attempting to generate Purkinje cells from human ES cells,” says Sasai. “This technology would be useful in establishing an in vitro disease model for spinocerebellar ataxia, to investigate its pathogenesis and to explore the possibility of gene therapy for this genetic disease.”
The corresponding author for this highlight is based at the Laboratory for Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology
Muguruma, K., Nishiyama, A., Ono, Y., Miyawaki, H., Mizuhara, E., Hori, S., Kakizuka, A., Obata, K., Yanagawa, Y., Hirano, T. & Sasai, Y. Ontogeny-recapitulating generation and tissue integration of ES cell-derived Purkinje cells. Nature Neuroscience 13, 1171–1180 (2010)
gro-pr | Research asia research news
Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University
Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
27.03.2017 | Earth Sciences
27.03.2017 | Life Sciences
27.03.2017 | Life Sciences