Summary: New research from Harvard Medical School shows that skin-derived signals—not preset genetic programming—direct sensory nerve endings to mature into the forms needed for specific types of touch on hairy or hairless skin.
The study reveals that cues from the skin itself determine whether mechanosensory neurons form high-acuity endings found in hairless areas or the distinct endings associated with hairy skin. If validated by further studies, these findings could inform strategies to regenerate damaged sensory nerves or clarify mechanisms underlying congenital sensory neuropathies.
Key Facts:
- Skin-derived signals, rather than an intrinsic predetermined fate, guide how sensory neurons develop their specialized endings.
- The same sensory neuron can produce different terminal structures—Meissner corpuscles in hairless (glabrous) skin and lanceolate endings in hairy skin—depending on the local skin environment.
- Bone morphogenetic proteins BMP5 and BMP7 are enriched in hairless skin and are required for normal development of Meissner corpuscles.
Source: Harvard Medical School
Overview: A team led by researchers at Harvard Medical School reports that mechanosensory nerve endings take their final form in response to signals from the skin region they innervate. Published in Developmental Cell on Aug. 21, the paper shows that skin type—glabrous versus hairy—plays an instructive role in shaping neuronal morphology, size, and structure rather than those features being fixed when the neuron is born.
Mechanosensory neurons, which provide our sense of touch, project axons from cell bodies near the spinal cord out to the skin. At their target, axons elaborate specialized terminals called end organs that match the sensory role required for that skin area. For example, low-threshold mechanoreceptors (LTMRs) that terminate in glabrous skin form Meissner corpuscles, structures tuned for high touch acuity on surfaces such as palms and soles. By contrast, LTMRs in hairy skin form longitudinal lanceolate endings around hair follicles, which are adapted to detect broad mechanical stimuli like brushing or wind.
Using mice as a model, the researchers tracked sensory neuron development from late embryonic stages through early postnatal life. Genetic labeling allowed visualization of single neurons as they extended into different skin domains. In the embryo, neurons destined for glabrous or hairy skin were morphologically similar, but within a week after birth their endings diverged to match the local skin type. This timing coincides with maturation of the skin itself, suggesting the target tissue provides instructive cues.
Compelling evidence came from neurons that branched across the border between glabrous and hairy skin: branches from the same cell body developed Meissner corpuscles in glabrous territory and lanceolate endings in hairy territory. In a separate experiment, a genetic mutation that produced ectopic glabrous skin on the tops of mouse paws led to formation of Meissner corpuscles in those normally hairy regions, further supporting a skin-driven mechanism.
To identify specific molecular signals, the team examined candidate factors and found that BMP5 and BMP7—members of the bone morphogenetic protein family—are expressed at higher levels in glabrous skin. Disrupting neuronal receptors for BMP signaling markedly reduced the number of Meissner corpuscles and produced aberrant morphology in those that remained, indicating BMP signaling is necessary for proper Meissner corpuscle development. The study did not, however, identify a parallel molecular trigger for lanceolate ending formation.
Together, the findings indicate that mechanoreceptor morphogenesis is flexible and instructed by the properties of the target tissue. This plasticity has practical implications: knowing that skin-derived cues can guide terminal differentiation of sensory neurons may help design approaches for regenerating or repairing sensory innervation after injury or disease. It may also inform research into congenital sensory neuropathies—disorders present from birth that impair touch perception—by revealing how target-derived signals influence neuronal fate.
David Ginty, chair of the Department of Neurobiology at the Blavatnik Institute at Harvard Medical School and a Howard Hughes Medical Institute investigator, is the study’s senior author. The work was led by Charalampia Koutsioumpa, formerly a graduate student in the Ginty Lab and now a neurology resident at Yale Medicine. The team emphasizes that further research is needed to translate these basic insights into therapies.
Authorship and funding
Additional authors: Celine Santiago, Kiani Jacobs, Brendan P. Lehnert, Victor Barrera, John N. Hutchinson, Dhane Schmelyun, Jessica A. Lehoczky, and David L. Paul.
Funding: Supported by a Boehringer Ingelheim Fonds fellowship, an Onassis Scholarship, the Harvard Medical School Foundry Program, and an NIH grant (R35 5R35NS097344-05).
About this neuroscience research news
Author: Ekaterina Pesheva ([email protected])
Source: Harvard Medical School
Contact: Ekaterina Pesheva – Harvard
Image: Image credited to Neuroscience News
Original Research: Open access. “Skin-type-dependent development of murine mechanosensory neurons” by David Ginty et al., published in Developmental Cell. DOI: 10.1016/j.devcel.2023.07.020
Abstract
Skin-type-dependent development of murine mechanosensory neurons
Mechanosensory neurons that innervate the skin enable the sense of touch. Rapidly adapting mechanoreceptors that innervate glabrous (non-hairy) skin form Meissner corpuscles, while in hairy skin they associate with hair follicles to form longitudinal lanceolate endings. How mechanoreceptors build axonal endings suited to each skin type has been unclear.
This study reports that mechanoreceptor morphologies are indistinguishable during early development and only diverge after birth as the skin matures. Neurons terminating along the border between glabrous and hairy skin show hybrid morphologies, with both Meissner corpuscles and lanceolate endings. Molecular profiles of neonatal neurons destined for glabrous versus hairy skin largely overlap. In mice with ectopic glabrous skin, mechanosensory neurons form end organs appropriate to the altered skin type. BMP5 and BMP7 are enriched in glabrous skin, and signaling through type I BMP receptors in neurons is critical for Meissner corpuscle morphology. These results indicate that mechanoreceptor morphogenesis is flexibly instructed by the target tissue.