Functional motor neuron subtypes generated from embryonic stem cells

Sep 02, 2010

Scientists have devised a method for coaxing mouse embryonic stem cells into forming a highly specific motor neuron subtype. The research, published by Cell Press in the September 3rd issue of the journal Cell Stem Cell, provides new insight into motor neuron differentiation and may prove useful for devising and testing future therapies for motor neuron diseases.

Motor neurons in the spinal cord communicate with other neurons in the and send long projections out to muscles, transmitting signals that are essential for proper control of movement and posture. Like other neuron classes, motor neurons are known to exhibit tremendous diversity. "The existence of dozens of muscle groups in the limbs of most mammals demands an equivalent diversity of motor neuron pool subtypes," explains the senior study author, Dr. Hynek Wichterle from Columbia University in New York.

During normal development, motor neurons settle into specific sections of the (called columns), which correspond to the muscles that they will innervate. For example, cells in one area link up with muscles in the limbs, while cells residing in another region innervate muscles in the body wall. Although previous studies have shown that mouse and human can be converted into motor neurons, it was not clear whether these were "generic" neurons or whether they could acquire characteristics of the specific specialized subtypes.

In the current study, lead author Dr. Peljto and colleagues showed that removing a key differentiation factor allowed cultured embryonic stem cells to form motor neurons with molecular characteristics corresponding to a limb innervating subtype, without the need for or added factors. Importantly, when this stem cell-derived subtype was transplanted into embryonic chick spinal cords, the motor neurons settled in the expected columnar position within the cord and had projections that mimicked the trajectory of limb innervating motor neurons.

Although encouraging from a regenerative medicine perspective, the authors caution that due to differences in limb and wing musculature, their mouse-to-chick transplantation paradigm makes it impossible to determine whether generated in the lab exhibit subtype specific connectivity with limb muscles. However, this method for reliably generating defined motor neuron subtypes may prove to be invaluable for future disease modeling studies.

"Motor neuron subtypes exhibit differential susceptibility to neurodegeneration in two prominent motor neuron diseases, Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA)," says Dr. Wichterle. "The ability to drive the differentiation of embryonic stem cells into disease-sensitive and -resistant motor neuron subtypes could help to uncover new therapeutic strategies."

Explore further: Scientists discover gene controlling muscle fate

add to favorites email to friend print save as pdf

Related Stories

Researchers generate functional neurons from somatic cells

Feb 24, 2009

In a new study, researchers were able to generate functionally mature motor neurons from induced pluripotent stem (iPS) cells, which are engineered from adult somatic cells and can differentiate into most other cell types. ...

Mixing and matching genes to keep nerve cells straight

Jun 09, 2008

With fewer than 30,000 human genes with which to work, Nature has to mix and match to generate the myriad types of neurons or nerve cells needed to assemble the brain and nervous system. Keeping this involved process on the ...

Recommended for you

Scientists discover gene controlling muscle fate

10 minutes ago

Scientists at the University of New Mexico have moved a step closer to improving medical science through research involving muscle manipulation of fruit flies. They discovered in the flight muscles of Drosophila ...

Study clues to aging bone loss

16 minutes ago

In Canada, bone fractures due to osteoporosis affect one in three women and one in five men over their lifetimes, costing the health care system more than $2.3 billion a year.

Sweat-eating bacteria may improve skin health

14 hours ago

Bacteria that metabolize ammonia, a major component of sweat, may improve skin health and some day could be used for the treatment of skin disorders, such as acne or chronic wounds. In a study conducted by AOBiome LLC, human ...

User comments : 0