Sixth sense genes

“Its job is to collect information from the muscles and joints about our movements, our posture and our position in space, and then transmit them to the central nervous system,” explains Dr. Niccolò Zampieri, head of the Development and Function of Neural Circuits of the Max Delbrück Center in Berlin. “This sense, known as proprioception, is what allows the central nervous system to send the right signals to the muscles via motor neurons so that they can perform a specific movement.”

 

This sixth sense – which, unlike the other five, is completely unconscious – is what prevents us from falling in the dark and allows us to bring a cup of coffee to our mouths with our eyes closed in the morning. But that’s not all: “People without proprioception are unable to perform coordinated movements,” says Zampieri. He and his team have now published a paper in the journal Nature Communications, in which they describe the molecular markers (variable DNA sequences that are inherited in a Mendelian fashion) of cells involved in this sixth sense. The findings should help researchers better understand the functioning of proprioceptive sensory neurons ( NSp ).

The cell bodies of NSp are found in the roots of the spinal cord. They are connected by long nerve fibers to the muscle spindles and Golgi tendon organs which, made up of free nerve endings, are interwoven between collagen fibers within a connective tissue capsule. The Golgi organs are located at the junction between tendons and muscle fibers and constantly record the stretch and tension of every muscle in the body. NSps send this information to the central nervous system, where it is used to control the activity of motor neurons so that movements can be performed.

“A prerequisite for this is that the NSp connect precisely to the different muscles of our body,” explains Dr. Stephan Dietrich, a member of Zampieri’s laboratory. However, almost nothing was known about the molecular programs that enable these precise connections that give muscle-specific NSp their unique identity. “For this reason we used our study to search for molecular markers that differentiate NSp for abdominal, back and limb muscles in mice,” explains Dietrich, lead author of the study, conducted at the Max Delbrück Center.

 

Guide to nascent nerve fibers

Using single cell sequencing, the team investigated which genes in the NSp of the abdominal, back and leg muscles are read and translated into RNA. “We found characteristic genes for NSp linked to each muscle group,” Dietrich explains. “We also demonstrated 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 the 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 developing nervous system,” Dietrich explains. The team found that the connections between the proprioceptors and the hindpaw muscles are impaired in mice that are unable to produce ephrin-A5.

“The markers we identified should help us further study the development and function of individual muscle-specific sensory networks,” Dietrich explains. “With optogenetics, for example, we can use light to turn 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 benefit patients, such as those with spinal cord injuries. “Once we better understand the details of proprioception, we will be able to optimize the design of neuroprostheses , which replace sensory or motor skills impaired by an injury,” explains Zampieri.

  • Molecular identity of proprioceptor subtypes innervating different muscle groups in mice (nature.com)
 

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