Unraveling the ins and outs of brain development

June 10, 2011
Figure 1: Cell nuclei of brain cells accumulate at the outer surface of the ventricular zone when the cell cycle is blocked. Credit: Reproduced from Ref. 1 2011 Yoichi Kosodo et al.

The embryonic nervous system is a hollow tube consisting of elongated neural progenitor cells, which extend from the inner to the outer surface of the tube. In a section inside the tube called the ventricular zone (VZ), these cells divide and produce immature neurons that migrate outwards. This involves well-characterized movements that are coupled to cell division. After a cell divides at the inner-most VZ region, the nuclei migrate to the outer region, where they synthesize new DNA before returning. 

To determine how the direction of movement is coupled to the cell division cycle, Yoichi Kosodo and colleagues in Matsuzaki's group at RIKEN Center for Developmental Biology labeled nuclei in the embryonic mouse brain with green fluorescent protein. This enabled them to not only track their movements in cultured brain slices using a video-imaging system, but also correlate their positions with phases of the cell cycle. They found that outward nuclear migration involves back and forth ‘ratcheting’ motions and occurs more slowly than inward migration. 

Importantly, they discovered that blocking the cell cycle before synthesis caused nuclei to accumulate at the outer VZ surface (Fig.1), and reduced outward migration. Nuclei migrating back inwards normally crowd out those just finished dividing, thus pushing them away from the inner VZ surface.

Examining their results further, the researchers computationally modeled nuclear migration, and incorporated fluorescent magnetic beads into the inner VZ surface. They observed the beads moving away from the inner VZ surface, and remaining at its outer region.

The researchers also showed that inward migration is closely linked to microtubule reorganization orchestrated by a protein called Tpx2, which is initially expressed in the nuclei of progenitors before moving to the mitotic spindle. This separates newly duplicated chromosomes. Translocation of Tpx2 to the cell region nearest the inner VZ surface promotes migration of the nucleus in that direction by microtubule re-organization. Reducing Tpx2 activity lowered the velocity of inward migration, but introducing the human Tpx2 gene into the lacking Tpx2 restored normal speed.

The researchers conclude that two mechanisms maintain brain structure during development. One couples cell migration to the , and occurs independently of other cells, with Tpx2 providing an active driving force; and the other involves interactions between the in the VZ.

Explore further: Key regulator of nervous system development works by blocking signaling protein

More information: Kosodo, Y., et al. Regulation of interkinetic nuclear migration by cell cycle-coupled active and passive mechanisms in the developing brain. The EMBO Journal 30, 1690–1704 (2011).

Related Stories

Key regulator of nervous system development works by blocking signaling protein

April 29, 2011
Neuroepithelial stem cells, the early progenitors for much of the nervous system, need to maintain a keen sense of direction in order to properly manage replication, migration and maturation. These cells are highly polarized, ...

Brain cell migration during normal development may offer insight on how cancer cells spread

April 24, 2011
By shedding new light on how cells migrate in the developing brain, researchers at Fred Hutchinson Cancer Research Center also may have found a new mechanism by which other types of cells, including cancer cells, travel within ...

Recommended for you

The neural codes for body movements

July 21, 2017
A small patch of neurons in the brain can encode the movements of many body parts, according to researchers in the laboratory of Caltech's Richard Andersen, James G. Boswell Professor of Neuroscience, Tianqiao and Chrissy ...

Faulty support cells disrupt communication in brains of people with schizophrenia

July 20, 2017
New research has identified the culprit behind the wiring problems in the brains of people with schizophrenia. When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia ...

Scientists reveal how patterns of brain activity direct specific body movements

July 20, 2017
New research by Columbia scientists offers fresh insight into how the brain tells the body to move, from simple behaviors like walking, to trained movements that may take years to master. The discovery in mice advances knowledge ...

Scientists discover combined sensory map for heat, humidity in fly brain

July 20, 2017
Northwestern University neuroscientists now can visualize how fruit flies sense and process humidity and temperature together through a "sensory map" within their brains, according to new research.

Team traces masculinization in mice to estrogen receptor in inhibitory neurons

July 20, 2017
Researchers at Cold Spring Harbor Laboratory (CSHL) have opened a black box in the brain whose contents explain one of the remarkable yet mysterious facts of life.

Speech language therapy delivered through the Internet leads to similar improvements as in-person treatment

July 20, 2017
Telerehabilitation helps healthcare professionals reach more patients in need, but some worry it doesn't offer the same quality of care as in-person treatment. This isn't the case, according to recent research by Baycrest.

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.