Motor neurons are responsible for transmitting signals from the spinal cord to muscles, enabling muscle contraction. The major principle of the motor system is that motor control requires sensory input to accurately execute movement. Necessary components of proper motor control are determined by adaptability, compensation for the physical characteristics of the body and muscles, coordination of signals to many muscle groups, proprioception, postural adjustments, sensory feedback, unconscious processing and volition.
A neuron is a highly specialised cell of the nervous system that has two characteristic properties: irritability (ability to be stimulated) and conductivity (ability to conduct impulses). Neurons that receive stimuli from the outside environment and transmit them toward the brain are called afferent or sensory neurons. Those that carry impulses in the opposite direction, away from the brain and other nerve centres to muscles, are called efferent neurons, or motor neurons. Another type, the interneuron, found in the brain and spinal cord, conducts impulses from afferent to efferent neurons.
The dendrites of the sensory neurons are designed to receive stimuli from various parts of the body. These dendrites are called receptor end organs and are of three general types: exteroceptors, interoceptors, and proprioceptors. The exteroceptors are located near the external surface of the body; receive impulses from the skin, and transmit information about the senses of touch, heat, cold, and other factors in the external environment. The interoceptors are located in the internal organs and receive information from the internal organs, e.g., pressure, tension, and pain. The proprioceptors are found in muscles, tendons, and joints and transmit “muscle sense,” by which one is aware of the position of one’s body in space. The point at which an impulse is transmitted from one neuron to another is called a synapse.
Understanding Motor Neuron Disease
Motor Neuron Disease (MND) is the name given to the group of neurodegenerative diseases in which the motor neurons fail to work or undergo degeneration and die in which it causes rapidly progressive muscle weakness. The disease affects nerve cells (motor neurons) that control the muscles that enable you to move, speak, breathe and swallow. Muscles then gradually weaken and waste, as neurons degenerate and die. Amyotrophic Lateral Sclerosis (ALS), Progressive Muscular Atrophy (PMA), Progressive Bulbar Palsy (PBP) and Primary Lateral Sclerosis (PLS) are all subtypes of motor neuron disease. Amyotrophic lateral sclerosis (ALS), also known as the Lou Gehrig’s disease, is the most well known motor neuron disease
In order to treat these diseases, scientists are developing methods to generate new, healthy motor neurons from stem cells. Researchers report they can generate human motor neurons from stem cells much more quickly and efficiently than previous methods allowed. A recent study has elucidated the cellular mechanisms that control the motor neuron differentiation, paving the way for new treatments for motor neuron diseases. Motor neuron damage in ALS leads to progressive muscle weakness that affects all parts of the body, impairing the ability to speak, swallow, and eventually breathe. Most people with ALS die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. However, about 10 percent of people with ALS survive for 10 or more years. Scientists aim to develop gene therapies or these diseases that can repair the damaged motor neurons and improve the functioning and lifespan of patients.
Gene Therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. To do this, they must first understand the signals that induce motor neuron development from stem cells. Stem cells are the precursors for every type of cell in the body. Stem cells have the potential to develop into many different cell types in the body during growth. They are triggered to differentiate into various cell types via cellular signalling molecules called transcription factors, which act on DNA to turn on specific genes. Which genes are turned on will determine the phenotypic fate of each cell. Typically, each cell goes through several stages of development before reaching its final fate.
A group of researchers from several universities recently discovered that a group of transcription factors of Protein Coding gene called the NIL factors – Ngn2(Neurogenin 2), Isl1(Insulin Gene Enhancer Protein), and Lhx3(LIM/homeobox protein) can induce motor neuron development from embryonic stem cells without passing through any of the intermediate stages. It is usually a four stage protocol to generate spinal motor neurons from human embryonic stem cells and human induced pluripotent stem cells. These stages include the pluripotent stem cell stage, neural stem cell stage, OLIG2 expressing motor neuron precursor stage, and HB9 expressing mature-MN stage. Moreover, the NIL factors achieved the transition to the motor neuron fate with a 90% success rate, and the process took only two days.
It can be achieved both in vitro and in living organisms at the site of cell damage.In the current study published in the journal Cell Stem Cell, Esteban Mazzoni and colleagues further investigated the process by which transcription factors bind to and activate parts of DNA during the first 48 hours after NIL expression. First, the researchers used single-cell RNA sequencing (RNA-seq) to study the timing of gene expression after induction by NIL programming factors. The researchers also studied chromatin remodelling during motor neuron programming. To study this chromatin remodelling process, a ChIP-seq time series was performed. In addition, the researchers used an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) to study chromatin accessibility.
This series of experiments revealed information about how genes are turned on and off over the 48-hour process of motor neuron formation. These experiments showed that the activities of Ngn2 and Isl1/Lhx3 act in tandem to induce direct motor neuron programming from stem cells. The researchers hope to apply these findings by triggering this programming pathway in the body. Cells in the spinal cord can be induced to differentiate into motor neurons, replacing the neurons that are damaged in diseases such as ALS.
H/T: Brain Blogger