Sensory Neurons in Skin linked with Pigmentation

Pigmentation in our skin is caused in part by a group of substances known as melanin, which are produced by skin cells called melanocytes. When melanocytes are damaged or reduced in number, this leads to either increased or limited melanin production, resulting in pigmentation disorders. Typically, these melanin changes are long term, localized, and uneven , such as skin color patches. The mechanisms that underpin the maintenance and development of these patches are mostly unknown.

Pigmentation disorders occur when extra or insufficient melanin is produced through damaged or decreased melanocytes. In most pigmentation disorders, changes of melanin are uneven, localized, and long-lasting, e.g., skin color patches. Skin color patches can be congenital or acquired with age. For instance, solar/senile lentigines are commonly acquired hyperpigmented skin patches, which are characterized by stable and local pigmentation with defined edges. They are widely believed to be triggered by repeated UV exposure; however, underlying mechanisms for development and maintenance of the local and stable color patches are largely unknown.

In contrast, the role of cutaneous sensory neurons in skin pigmentation has not been explored. Sensory inputs on skin have a sensory acuity of a couple of centimeters, coinciding with the size of common skin color spots. While effects of diverse cell types on neuronal activities and physiology (e.g., pain and itch) are well studied, the contribution of neurons to skin cells has not been studied extensively. Interestingly, neurocutaneous diseases, such as tuberous sclerosis, are congenital syndromes characterized by neurological symptoms and skin color patches. This pathological association indicates a functional link between skin patches and neurons. Importantly, melanocytes and neurons share the same developmental origin and are both derived from neural crest cells.

A research group has found that sensory neurons play an important role in human skin pigmentation and physiology.

In their study, the researchers explored the relationship between sensory neurons and melanocytes, and found that there was a greater degree of contact between them in skin color patch tissue than control tissue. When cultured with neurons, melanocytes were also found to have higher pigmentation and an increased survival rate. Melanocytes cultured in growth media that had been conditioned with sensory neurons showed increased survival, as well as longer dendrites (branch-like extensions of the cell); these effects were specific to melanocytes.

The study revealed that sensory neurons play a role in modulating a number of features of human melanocytes via the secretion of RGMB, which is a key factor that stimulates melanocytes.

Pigmentation disorders, including skin color patches, are common and can result in psychosocial problems; they are also often linked with health issues such as neurocutaneous diseases (diseases that affect the nervous system and skin) and melanoma. However, the effectiveness of chemical and topical treatments for these are limited. The results of this study could lead to the development of new drugs for use with current therapies by enabling the discovery of previously unknown molecules and mechanisms that include RGMB.


Siu Yu A. Chow, Kazuki Nakayama, Tatsuya Osaki, Maki Sugiyama, Maiko Yamada, Hirotaka Takeuchi, Yoshiho Ikeuchi, (September 20, 2022). Human sensory neurons modulate melanocytes through secretion of RGMB. Cell Reports. Retrieved from :