Navigation Links
Neurons find their place in the developing nervous system with the help of a sticky molecule

The brain, that exquisite network of billions of communicating cells, starts to take form with the genesis of nerve cells. Most newborn nerve cells, also called neurons, must travel from their birthplace to the position they will occupy in the adult brain. Researchers at the Salk Institute for Biological Studies have identified a molecule expressed on the surface of certain migrating neurons that helps them find their correct position along on the way.

Decreasing levels of that protein, an adhesion molecule called MDGA1, prevents neurons that normally make this protein from assuming their proper position, resulting in brain malformation, researchers report in the April 26th issue of the Journal of Neuroscience.

As Dennis D. M. O'Leary, Ph.D., senior author of the study and a Professor in the Molecular Neurobiology Laboratory put it, "proper neuronal positioning is essential for development of appropriate wiring, which is in turn critical for establishing a normal, functioning nervous system."

Neurons migrate throughout the brain, but migration is particularly important for development of part of the brain known as the cerebral cortex. The cortex sits like a skullcap over the rest of the brain and is responsible for sensory perception, higher-level reasoning, and, in humans, language. In mammals, the largest and evolutionarily newest part of the cortex, the neocortex, is recognized anatomically by its six horizontal layers.

The neocortex develops outward from an underlying zone of cells. From that zone, crawling neurons migrate radially out toward the surface or "superficial" part of the developing cortex, giving rise to a laminar structure. Neurons forming layers 2 and 3, the focus of the current study, are born last and so must elbow their way through cells lying in earlier formed layers to reach what will become the outermost layers. Without MDGA1, these neurons begin to migrate but get stuck before they reach their normal destina tion.

The MDGA1 gene was cloned and characterized first in rat by O'Leary and two former postdoctoral fellows, E. David Litwack, Ph.D. and Matthias Gesemann, Ph.D. They showed that MDGA1 is a cell adhesion molecule ?a protein enabling cells to attach to other surfaces, something that they must do either to move or sit still and elaborate connections. They also showed that MDGA1 is expressed on subpopulations of migrating neurons throughout the developing nervous system, including layer 2/3 neurons in the neocortex, suggesting that MDGA1 may actually be required for migration.

In the current study, O'Leary and Akihide Takeuchi, M.D., Ph.D., a postdoctoral fellow and the study's first author, tested this hypothesis. They first showed that layer 2/3 neurons make MDGA1 protein as they migrate to their destination. Then, utilizing a cutting-edge molecular technique called RNA interference, the Salk researchers silenced the MDGA1 gene. To do this, they painstakingly performed in utero surgery on embryonic mice ?injecting an interfering RNA molecule into the lateral ventricle, a fluid-filled space next to the neocortex. Application of an electrical current forced the RNA into neural progenitor cells, and it was subsequently inherited by their neuronal progeny that form layer 2/3 and blocked their ability to make MDGA1 protein.

When Takeuchi and O'Leary examined the neocortex a few days later when the mice were born, they discovered that nearly all neurons containing the interfering RNA were stalled in aberrant deeper locations, indicating that loss of MDGA1 protein had stymied their attempt to travel the full distance to layer 2/3 and supporting the original hypothesis. The goal now is to determine how MDGA1 controls neuronal migration and what the long-term consequences are of its loss.

Impaired function of neuronal adhesion molecules has been previously linked to neurological defects in humans. A cell adhesion molecule known as L1 has been shown to affect cell migration and positioning in other parts of the nervous system. Numerous mutations in the human L1 gene have been uncovered; individuals with these mutations often show severe defects in neuronal positioning and connectivity, which are clinically manifested in conditions such as hydrocephalus, mental retardation and spastic paraplegia.

Whether mutations in MDGA1 lead to brain disorders remains to be seen. "Much work needs to be done, and the appropriate tools need to be developed to do this work," said O'Leary, "but we feel that these studies will eventually provide insight into neurological disorders that have their basis in malpositioning of neurons."


Source:Salk Institute

Related biology news :

1. Neurons generated in the adult brain learn to respond to novel stimuli
2. Neurons grown from embryonic stem cells restore function in paralyzed rats
3. Priming embryonic stem cells to fulfill their promise
4. Protein offers way to stop microscopic parasites in their tracks
5. Flocking together: Study shows how animal groups find their way
6. Where bacteria get their genes
7. Chickadees can help humans get their bearings
8. Bacteria use hosts immune response to their competitive advantage
9. Structures of marine toxins provide insight into their effectiveness as cancer drugs
10. Beauty queens urge girls not to sacrifice their bones
11. Researchers learn how blood vessel cells cope with their pressure-packed job
Post Your Comments:

(Date:11/17/2015)... -- Vigilant Solutions announces today that Mr. Dick W. ... --> --> Mr. Boyce ... at TPG Capital, one of the largest global investment ... revenue.  He founded and led TPG,s Operating Group, which ... 1997 to 2013.  In his first role, he served ...
(Date:11/12/2015)...   Growing need for low-cost, easy to ... paving the way for use of biochemical sensors ... in clinical, agricultural, environmental, food and defense applications. ... medical applications, however, their adoption is increasing in ... emphasis on improving product quality and growing need ...
(Date:11/9/2015)...  Synaptics Inc. (NASDAQ: SYNA ), the leading ... into the automotive market with a comprehensive and dedicated ... consumer electronics human interface innovation. Synaptics, industry-leading touch controllers, ... automotive industry and will be implemented in numerous locations ... , Japan , and ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... 2015  PharmAthene, Inc. (NYSE MKT: PIP) announced  today ... rights plan (Rights Plan) in an effort to preserve ... under Section 382 of the Internal Revenue Code (Code). ... use of its NOLs could be substantially limited if ... Section 382 of the Code. In general, an ownership ...
(Date:11/25/2015)... HOLLISTON, Mass. , Nov. 25, 2015 ... a biotechnology company developing bioengineered organ implants for life-threatening ... will present at the LD Micro "Main Event" investor ... PT. The presentation will be webcast live and posted ... also be available at the conference for one-on-one meetings ...
(Date:11/25/2015)... Muncie, IN (PRWEB) , ... November 25, 2015 ... ... Aeronautics (AMA) and the Organization of Black Aerospace Professionals (OPBAP) has been formalized ... Mathewson and other AMA team leaders met with OPBAP leaders Capt. Karl Minter ...
(Date:11/25/2015)... ... November 25, 2015 , ... Jessica Richman and Zachary ... in their initial angel funding process. Now, they are paying it forward to ... early stage investments in the microbiome space. In this, they join other ...
Breaking Biology Technology: