Summary: Study identifies genetic markers in cells associated with proprioception. The findings provide new clues about how proprioceptive sensory neurons help control movement.
Source: Center Max Delbruck
To perform coordinated movements, we rely on special sensory neurons in our muscles and joints. Without them, the brain wouldn’t know what the rest of our body is doing.
A team led by Niccolò Zampieri studied their molecular markers to better understand how they work and described the results in Nature Communication.
Sight, hearing, smell, taste, touch: we all know the five senses that allow us to feel our environment.
Equally important but much less known is the sixth sense: “Its role is to collect information from muscles and joints about our movements, our posture and our position in space, then transmit them to our central nervous system”, explains Dr. Niccolò Zampieri, head of the laboratory for the development and functioning of neural circuits at the Max Delbrück Center in Berlin.
“This sense, known as proprioception, is what allows the central nervous system to send the right signals through the motor neurons to the muscles so that we can perform a specific movement.”
This sixth sense – which, unlike the other five, is entirely unconscious – is what keeps us from falling into the dark and allows us to bring a cup of coffee to our mouth with our eyes closed in the morning.
But that’s not all: “People without proprioception can’t actually perform coordinated movements,” says Zampieri. He and his team have just published an article in which they describe the molecular markers of the cells involved in this sixth sense. The findings should help researchers better understand how proprioceptive sensory neurons (pSN) work.
Accurate connections are crucial
pSN cell bodies are located in the dorsal root ganglia of the spinal cord. They are connected by long nerve fibers to the muscle spindles and Golgi tendon organs which constantly register stretch and tension in every muscle in the body.
The pSN sends this information to the central nervous system, where it is used to control the activity of motor neurons so that we can perform movements.
“A prerequisite for this is that the pSN connects precisely to the different muscles in our body,” says Dr. Stephan Dietrich, a member of Zampieri’s lab. However, almost nothing was known about the molecular programs that enable these precise connections and give the muscle-specific pSN its unique identity.
“That’s why we used our study to search for molecular markers that differentiate pSN from abdominal, back and limb muscles in mice,” says Dietrich, lead author of the study, which was performed at the Max Delbrück Center.
Guidance for nascent nerve fibers
Using single-cell sequencing, the team studied which genes in pSN from abdominal, back and leg muscles are read and translated into RNA. “And we found characteristic genes for the pSN connected to each muscle group,” says Dietrich.
“We also showed that these genes are already active in the embryonic stage and remain active for at least some time after birth.” Dietrich explains that this means that there are fixed genetic programs that decide whether a proprioceptor will innervate abdominal, back or limb muscles.
Among their findings, the Berlin researchers identified several genes for ephrins and their receptors. “We know that these proteins are involved in guiding nascent nerve fibers to their target during the development of the nervous system,” says Dietrich. The team found that connections between proprioceptors and back leg muscles were impaired in mice that cannot produce ephrin-A5.
One goal is better neuroprostheses
“The markers we have identified should now help us to further investigate the development and function of sensory networks specific to individual muscles,” Dietrich says. “With optogenetics, for example, we can use light to switch proprioceptors on and off, individually or in groups. This will allow us to reveal their specific role in our sixth sense,” adds Zampieri.
This knowledge should eventually benefit patients, such as those with spinal cord injuries. “Once we better understand the details of proprioception, we can optimize the design of neuroprostheses, which support motor or sensory abilities that have been impaired by injury,” says Zampieri.
Altered muscle tension causes a twisted spine
He adds that researchers in Israel recently discovered that proper functioning of proprioception is also important for a healthy skeleton. Scoliosis, for example, is a condition that sometimes develops during growth in childhood and causes the spine to twist and twist.
“We suspect this is caused by dysfunctional proprioception, which alters muscle tension in the back and distorts the spine,” Zampieri says.
Hip dysplasia, an abnormality of the hip joint, can also be caused by faulty proprioception. This led Zampieri to envision another research outcome: “If we can better understand our sixth sense, it will be possible to develop new therapies that effectively counteract these and other types of skeletal injuries.”
About this genetics and neuroscience research news
Author: Press office
Source: Center Max Delbruck
Contact: Press service – Center Max Delbruck
Image: The image is attributed to Stephan Dietrich, Zampieri Lab, Max Delbrück Center
Original research: Free access.
“Molecular identity of proprioceptor subtypes innervating different muscle groups in mice” by Stephan Dietrich et al. Nature Communication
Molecular identity of proprioceptor subtypes innervating different muscle groups in mice
The precise execution of coordinated movements depends on proprioception, the sense of the body’s position in space. However, the molecular underpinnings of proprioceptive neuron subtype identities are not fully understood.
Here, we used a single-cell transcriptomic approach to define mouse proprioceptor subtypes based on the identity of the muscle they innervate.
We have identified and validated molecular signatures associated with proprioceptors innervating the back (Toxic, Epha3), abdominal (C1ql2) and hind limbs (gabrg1, Efna5) muscles. We also found that proprioceptor muscle identity precedes acquisition of receptor character and includes programs controlling wiring specificity.
These results indicate that muscle type identity is a fundamental aspect of proprioceptor subtype differentiation that is acquired during early development and includes molecular programs involved in the control of muscle target specificity.
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