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

Featured In: Cancer

Sunday, April 24, 2024

Get daily Bioscience Technology industry top stories and headlines - Sign up now!

newsvine diigo google
slashdot
Share
Loading...

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 the body. The findings by Jonathan Cooper, PhD, member and director of the Hutchinson Center’s Basic Sciences Division, and Yves Jossin, Ph.D., a research fellow in Cooper’s laboratory, published online April 24 in Nature Neuroscience, could lead to a better understanding of neurological development and, possibly, cancer metastasis.

During normal development cells divide, arrange themselves in appropriate patterns, and specialize to form discrete tissues and organs. For the body to develop properly, cells must coordinate their migratory patterns and the process by which they differentiate, or evolve from less-specialized cells into more-specialized cell types. A lack of such coordination leads to disordered development and, in some cases, cancer.

Neuron nuclei are labeled blue. Some normal neurons are tracked in green (they appear cyan in the image because they are labeled both blue and green). Many of them have reached the top of the cortex. Some abnormal neurons, in which the Reelin/N-cadherin pathway is blocked, are tracked in red (they appear yellow where they are superimposed on green, normal neurons). The abnormal neurons are blocked in the intermediate zone. (Source: Yves Jossin)

Jossin and Cooper set out to analyze how cells migrate in the cerebral cortex of the developing brain. The cerebral cortex, gray matter of the cerebrum, is the brain’s command and control center where cognition and planning occur, and it is particularly well developed in humans.

The cerebral cortex is composed of horizontal layers of nerve cells, or neurons, which are specialized for different functions and connected vertically into circuits. If some neurons are in the wrong layers, the wiring can be defective and neurological disorders including epilepsy, autism and schizophrenia may result.

In the fetus, the cortex grows "from the inside out" via the sequential addition of new neurons, which move from the inside, pass between neurons in previously established intermediate layers, and form new layers on the outside. How the migrations are regulated remains unclear despite years of study.

Jossin and Cooper now report the discovery of signals that control a particular stage in a cortical neuron’s journey. New neurons initially move in a straight line, from the inside to the outside, until they reach a layer called the intermediate zone. This zone contains relatively few neurons but many connecting fibers, or axons. When new neurons reach this layer, they lose their way and start wandering — up, down, left and right, frequently changing direction. When, seemingly by chance, they emerge from the intermediate zone, they realign with their original direction of movement and speed ahead through layers of differentiated neurons towards the outer surface of the cortex.

The researchers aimed to determine how neurons get back on track after they emerge from the chaos of the intermediate zone. They identified a signaling protein, called Reelin, which is made by cells in the outermost layer of the cortex. It has been known for years that mutations in the Reelin gene cause profound cortical layering abnormalities in rodents and people, but it has been unclear which stage of neuron migration goes awry when Reelin is absent.

The new study shows that new neurons respond to Reelin as they emerge from the intermediate zone. "This is remarkable because the top layer of the cortex, where Reelin is made, is widely separated from the top of the intermediate zone, where it acts, so the Reelin protein must be diffuse," Cooper said. "It is also remarkable that Reelin seems not to be a direction signal itself. Rather, Reelin triggers changes in the membranes of the migrating neurons that allow the cells to respond to direction signals."

The researchers show that a membrane protein called N-cadherin increases on the surface of neurons when the neurons encounter Reelin. The surface increase in N-cadherin allows the cell to choose the appropriate direction for its next stage of migration. "This represents a new and surprising function for N-cadherin," Jossin said, "because normally this protein acts as a cellular stabilizer and not as an orchestrator of migration."

For example, elsewhere in the cortex, N-cadherin forms tight adhesions between adjacent cells and prevents them from moving. Indeed, the general role for cadherins in the body is to stabilize sheets of cells and organize tissues by holding cells together.

"The new role for N-cadherin in orienting migrating cells is quite unexpected and suggests that cadherins on the surface of other types of normal or cancer cells may also be involved in helping them move rather than stay in place," Jossin said. "This finding could provide new clues to how normal and cancerous cells migrate within the body," he said.

Source: Fred Hutchinson Cancer Research Center

Join the Discussion
Rate Article: Average 0 out of 5
register or log in to comment on this article!

0 Comments

Add Comment

Text Only 2000 character limit

Page 1 of 1

Research Exchange

Bringing the Cell Image into Focus

Nov 2 2010

Improvements in transmission electron microscope (TEM) technology increase the power of this imaging tool for the study of cell biology.

Finding a Cure for Spinal Cord Injury with On-Demand LIMS

Oct 25 2010

The Miami Project to Cure Paralysis finds an on-demand laboratory information management system (LIMS) helps to accelerate discovery in its HCS projects.

Saving Cells: Image Processing for Improved Viability, Part II: Iterative Deconvolution

Oct 25 2010

3D light microscopy and deconvolution provide a means to investigate 3D structure, providing near-confocal quality images without the temporal requirements or potentially damaging phototoxicity associated with other 3D imaging technologies. This article is Part II in a series regarding viability, resolution improvement, and measurement in fluorescence imaging. Part I focused on spectral unmixing.

Saving Cells: Image Processing for Improved Viability

Sep 22 2010

This article is Part I of a two-part series regarding viability, resolution improvement, and measurement in fluorescence imaging. Part II will focus on deconvolution.

Evaluation of a New Nano-Type UV-Vis Spectrophotometer

Mar 3

Analysis of one- to four-microliter size samples for nucleic acids has become routine in many life science laboratories. However, until now, available instruments require considerable manipulation of the instrument and sample; some require manually recording the data. The user must typically lower and raise the arm manually, then wipe the sample manually from the target after each analysis. And fiberoptics used in some of these instruments are subject to deterioration.

Production of Recombinant Proteins and Monoclonal Antibodies in Hollow Fiber Bioreactors

Jan 25

While well-understood, robust and convenient, classical batch-style 2-D culture on non-porous supports or 3-D suspension culture in other devices are really not very biologically relevant models. Cell culture conditions can affect the quality of the antibody or protein produced.

Selecting Robots for Use in Drug Discovery and Testing

Dec 6 2010

Drug discovery and testing, with their need for speed, repeatability and verification, are ideally suited to benefit from robot automation. It is therefore not surprising that robots have been at the forefront of automation developments in both these areas.

HP Scalable Network Storage Systems for Life Sciences

Sep 13 2010

Life sciences research today is advancing exponentially, each step bringing us closer to the realization of truly personalized medicine–preventive care and treatments designed specifically for each individual. In the near future, PCPGM healthcare researchers expect to be able to use predictive genetic testing to create custom treatment plans for individuals and deliver dramatic improvements over today’s one-size-fits-all approach. But research capabilities are only part of the equation; current storage and operating capacities must also evolve to accommodate ever-expanding amounts of data before the goal of personalized medicine can be realized.

Using the Tecan Genesis Workstation to Automate a Cytometric Bead Array (CBA) Immunoassay

Mar 11 2010

The poster describe the process involved in automating a Cytometric Bead Array (CBA) immunoassay developed to measure relative concentrations of serum antibodies against Tetanus (TT), Sperm Whale Myoglobin (SWM) and Keyhole Limpet Hemocyanin (KLH) in KLH-immunized volunteers.

Ensuring Quality in Assays Performed with Automated Liquid Handlers

Feb 2 2010

The focus of this presentation is to highlight the need of ensuring quality in important assays performed with automated liquid handlers. Nearly all assays performed within a laboratory are volume-dependent. In turn, all concentrations of biological and chemical components in these assays, as well as the associated dilution protocols, are volume-dependent. Because analyte concentration is volume-dependent, an assay’s results might be falsely interpreted if liquid handler variability and inaccuracies are unknown or if the system(s) go unchecked for a long period.

Inkjet System for Protein Crystallography

Feb 1 2010

X-ray crystallography is used routinely by scientists to obtain the three dimensional structure of a biological molecule of interest.Such information can be used to determine how a pharmaceutical interacts with a protein target and what changes might improve functionality. However, the crystallization of macromolecules still remains a serious hindrance in structural determination despite impressive advances in screening methods and technologies.

Attention Deficit & Hyperactivity in a Drosophila Memory Mutant

Attention Deficit & Hyperactivity in a Drosophila Memory Mutant

Nov 9 2009

Action selection is modulated by external stimuli either directly or via memory retrieval. In a constantly changing environment, animals have evolved attention-like processes to effectively filter the incoming sensory stream. These attention-like processes, in turn, are modulated by memory. The neurobiological nature of how attention, action selection and memory are inter-connected is unknown. We describe here new phenotypes of the memory mutant radish in the fruit fly Drosophila.

Genome-Wide Analysis of Self-Renewal in Drosophila Neural Stem Cells by Transgenic RNAi

10 hours ago

The balance between stem cell self-renewal and differentiation is precisely controlled to ensure tissue homeostasis and prevent tumorigenesis. Here we use genome-wide transgenic RNAi to identify 620 genes potentially involved in controlling this balance in Drosophila...

Modeling lipid accumulation in oleaginous fungi in chemostat cultures: I. Development and validation of a chemostat model for Umbelopsis isabellina

15 hours ago

Lipid-accumulating fungi may be able to produce biodiesel precursors from agricultural wastes. As a first step in understanding and evaluating their potential, a mathematical model was developed to describe growth, lipid accumulation and substrate consumption of...

Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction

16 hours ago

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension and endothelial dysfunction. Several Nox isoforms are expressed in the vessel wall, among which Nox2 is especially abundant in the...

Increased Levels of Nuclear Factor κB and Fos-Related Antigen 1 in Lung Tissues From Patients With Acute Respiratory Distress Syndrome.

17 hours ago

Abstract Context.-Both nuclear factor κB and Fos-related antigen 1 have been implicated in the pathogenesis of inflammatory lung diseases, including acute lung injury/acute respiratory distress syndrome. Objective.-To evaluate lung tissues from patients with...

Prokariotic Cell Collection in Denmark

Nov 6 2009

I would like to know about a prokariotic cell collection in Denmark. Is there a cell bank in this country? I need a Lactobacillus strain for a fermentation assay and this information about the bank is very helpful for me.

Request for Entries

Oct 16 2009

Ask the Experts is your chance to get the answers to questions on applications, materials, methods, processes, and technologies. Email you question to bst_web@advantagemedia.com, and the editors of Bioscience Technology will find an appropriate expert to answer it. Watch this space in the future to see the questions your colleagues are posting.

STAY INFORMED: SUBSCRIBE TO

Magazine and E-mail Newsletters

Loading...
E-mail:   

MULTIMEDIA

Video:

Viewing SureFocus Slides

Jun 11 2010

A demonstration of SureFocus Microscope Slides in the review of AFB Smears. SureFocus Slides are a patent-pending breakthrough in tuberculosis detection, as their fluorescent staining circle remains visible during review, Fluorescence Microscopy.

Podcasts:

Allen Institute for Brain Research

Allen Institute for Brain Research

Oct 14 2009

Discussed in this interview are both the mouse brain project and the human cortex project with an emphasis on the importance of these projects to neuroscience research.

Top Stories and Headlines
EVERYDAY!

FREE Email Newsletter

Information: