Scientists at the Institute of Molecular Biology (IMB) in Mainz have unraveled a complex regulatory mechanism that explains how a single gene can drive the formation of brain cells. The research, published in The EMBO Journal, is an important step towards a better understanding of how the brain develops. It also harbors potential for regenerative medicine.
Neurodegenerative disorders, such as Parkinson's disease, are often characterized by an irreversible loss of brain cells. Unlike many other cell types in the body, these neurons are generally not able to regenerate by themselves, so if the brain is damaged, it stays damaged.
Cells in which NeuroD1 is turned on are reprogrammed to become neurons. Cell nuclei are shown in blue (Höchst stain) and neurons, with their characteristic long processes, are shown in red (stained with neuronal marker TUJ1).
Credits: A. Pataskar/J. Jung & V. Tiwari
Diagram showing how NeuroD1 influences the development of neurons. During brain development, expression of NeuroD1 marks the onset of neurogenesis. NeuroD1 accomplishes this via epigenetic reprogramming: neuronal genes are switched on, and the cells develop into neurons. (TF: transcription factor; V: ventricle; P: pial surface)
Credits: A. Pataskar/J. Jung & V. Tiwari
One hope of developing treatments for this kind of damage is to understand how the brain develops in the first place, and then try to imitate the process. However, the brain is also one of the most complex organs in the body, and very little is understood about the molecular pathways that guide its development.
Scientists in Dr. Vijay Tiwari's group at the Institute of Molecular Biology at Johannes Gutenberg University Mainz have been investigating a central gene in brain development, NeuroD1. This gene is expressed in the developing brain and marks the onset of neurogenesis.
In their research article, Tiwari and his colleagues have shown that during brain development NeuroD1 is not only expressed in brain stem cells but acts as a master regulator of a large number of genes that cause these cells to develop into neurons.
They used a combination of neurobiology, epigenetics, and computational biology approaches to show that these genes are normally turned off in development, but NeuroD1 activity changes their epigenetic state in order to turn them on. Strikingly, the researchers show that these genes remain switched on even after NeuroD1 is later switched off.
They further show that this is because NeuroD1 activity leaves permanent epigenetic marks on these genes that keep them turned on, in other words it creates an epigenetic memory of neuronal differentiation in the cell.
Abhijeet Pataskar and Johannes Jung, joint first authors on the paper, explained the significance of this discovery: "Our research has shown how a single factor, NeuroD1, has the capacity to change the epigenetic landscape of the cell, resulting in a gene expression program that directs the generation of neurons."
Dr. Vijay Tiwari is excited about the implications of these findings: "This is a significant step towards understanding the relationship between DNA sequence, epigenetic changes, and cell fate. It not only sheds new light on the formation of the brain during embryonic development but also opens up novel avenues for regenerative therapy."
Pataskar A*, Jung J*, Smialowski P, Noack F, Calegari F, Straub T and Tiwari VK (2015). NeuroD1 reprograms chromatin and transcription factor landscapes to induce the neuronal program. EMBO J, pii: e201591206. [Epub ahead of print]. (*indicates equal contribution)
News & Views by Glahs A, Zinzen RP (2015). Putting chromatin in its place: the pioneer factor NeuroD1 modulates chromatin state to drive cell fate decisions. EMBO J, Nov 13, DOI: 10.15252/embj.201593324
Further information about Dr. Vijay Tiwari’s research can be found at http://www.imb.de/tiwari.
About the Institute of Molecular Biology gGmbH
The Institute of Molecular Biology gGmbH (IMB) is a center of excellence in the life sciences that was established in 2011 on the campus of Johannes Gutenberg University Mainz (JGU). Research at IMB concentrates on three cutting-edge areas: epigenetics, developmental biology, and genome stability. The institute is a prime example of a successful collaboration between public authorities and a private foundation. The Boehringer Ingelheim Foundation has dedicated EUR 100 million for a period of ten years to cover the operating costs for research at IMB, while the state of Rhineland-Palatinate provided approximately EUR 50 million for the construction of a state-of-the-art building.
About the Boehringer Ingelheim Foundation
The Boehringer Ingelheim Foundation is an independent, non-profit organization committed to the promotion of the medical, biological, chemical, and pharmaceutical sciences. It was established in 1977 by Hubertus Liebrecht (1931-1991), a member of the shareholder family of the company Boehringer Ingelheim. With the PLUS 3 Perspectives Program and the Exploration Grants, the foundation supports independent group leaders. It also endows the internationally renowned Heinrich Wieland Prize as well as awards for up-and-coming scientists. In addition, the foundation pledged to donate EUR 100 million to finance the scientific running of the IMB at Johannes Gutenberg University Mainz for ten years. In 2013, the Boehringer Ingelheim Foundation donated a further EUR 50 million to Johannes Gutenberg University Mainz.
Petra Giegerich | idw - Informationsdienst Wissenschaft
Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex
New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences