A closer look at brain organoid development

March 10, 2017
Left hemisphere of J. Piłsudski's brain, lateral view. Credit: public domain

How close to reality are brain organoids, and which molecular mechanisms underlie the remarkable self-organizing capacities of tissues? Researchers already have succeeded in growing so-called "cerebral organoids" in a dish - clusters of cells that self-organize into small brain-like structures. Juergen Knoblich and colleagues have now further characterized these organoids and publish their results today in The EMBO Journal. They demonstrate that, like in the human brain, so-called forebrain organizing centers orchestrate developmental processes in the organoid, and that organoids recapitulate the timing of neuronal differentiation events found in human brains.

The development of the human brain from just a few cells to a thinking organ is one of the great mysteries of biology. In the past decade, Knoblich and his team at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences have pioneered brain organoid technology to investigate this intriguing process. Understanding normal organoid development is a prerequisite to using this powerful system to explore the possibility of modeling human developmental diseases.

The neocortex is the part of the mammalian brain involved in higher-order cognitive functions. It has expanded substantially in the course of the mammalian evolution and is highly complex in humans. Building such an intricate system relies on a precise orchestration of different developmental processes - the division of progenitor cells, and the generation of distinct cell types at the right time and the right place. So-called forebrain organizing centers play a key role in orchestrating the development of the neocortex. Organizing centers secrete factors that work long-distance to induce neighboring tissue to give rise to specific cell types. In normal brain development, an organizing center called the cortical hem lies just under the crown of the head, while the antihem marks the opposite side of the cortex and is located at the right and left side of the brain. The researchers found that both these organizing centers are present in organoids.

When the brain grows, new cells are added in a precise order. Cells formed earlier will differentiate into neurons of the inner layers of the cortex, while cells born later migrate further outwards, and glial cells - non-neural cells of the brain - are added towards the end. Finally, nerve cells grow long protrusions and connect with each other to form a complex network. These processes are also mimicked in brain organoids, stressing the value of organoids in investigating a broad array of .

In the past years, Knoblich and his team have already expanded their research on organoids towards growing them from patient to investigate the cellular basis of developmental disorders. However, a thorough knowledge of normal organoid development is required to be able to interpret the aberrations in an organoid model of a developmental disease. The detailed description of organoid development in the current study of Knoblich's laboratory is an important step in this direction.

Explore further: Study implicates neural stem cell defects in smooth brain syndrome

More information: "Self‐organized developmental patterning and differentiation in cerebral organoids," The EMBO Journal (2017) e201694700. DOI: 10.15252/embj.201694700

Related Stories

Study implicates neural stem cell defects in smooth brain syndrome

February 13, 2017
Research led by scientists at UC San Francisco and Case Western Reserve University School of Medicine has used brain "organoids"—tiny 3-D models of human organs that scientists grow in a dish to study disease—to identify ...

Scientists engineer gene pathway to grow brain organoids with surface folding

December 29, 2016
One of the most significant ways in which the human brain is unique is the size and structure of the cerebral cortex. But what drives the growth of the human cortex, likely the foundation for our unique intellectual abilities?

Building a better brain

December 20, 2016
When you build models, whether ships or cars, you want them to be as much like the real deal as possible. This quality is even more crucial for building model organs, because disease treatments developed from these models ...

Method to create kidney organoids from patient cells provides insights on kidney disease

November 17, 2016
A new method to create kidney organoids from patient cells may provide insights into how kidney diseases arise and how they should be treated. The research will be presented at ASN Kidney Week 2016 November 15¬-20 at McCormick ...

Zika virus reduces growth and induces cell death and malformations in human neurospheres and brain organoids

April 11, 2016
Brazilian researchers from the D'Or Institute for Research and Education (IDOR) and Federal University of Rio de Janeiro (UFRJ) have demonstrated the harmful effects of ZIKA virus (ZIKV) in human neural stem cells, neurospheres ...

Recommended for you

New approach helps rodents with spinal cord injury breathe on their own

October 17, 2017
One of the most severe consequences of spinal cord injury in the neck is losing the ability to control the diaphragm and breathe on one's own. Now, investigators show for the first time in laboratory models that two different ...

Pair of discoveries illuminate new paths to flu and anthrax treatments

October 17, 2017
Two recent studies led by biologists at the University of California San Diego have set the research groundwork for new avenues to treat influenza and anthrax poisoning.

New method to measure how drugs interact

October 17, 2017
Cancer, HIV and tuberculosis are among the many serious diseases that are frequently treated with combinations of three or more drugs, over months or even years. Developing the most effective therapies for such diseases requires ...

A new compound targets energy generation, thereby killing metastatic cells

October 17, 2017
Cancer can most often be successfully treated when confined to one organ. But a greater challenge lies in treating cancer that has metastasized, or spread, from the primary tumor throughout the patient's body. Although immunotherapy ...

Research finds that zinc binding is vital for regulating pH levels in the brain

October 17, 2017
Researchers in Oslo, Norway, have discovered that zinc binding plays an important role in the sensing and regulation of pH in the human brain. The findings come as one of the first studies that directly link zinc binding ...

Researchers find factor that delays wound healing

October 17, 2017
New research carried out at The University of Manchester has identified a bacterium—normally present on the skin that causes poor wound healing in certain conditions.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.