BMP Signaling Differentially Influences Glabrous Ending Morphogenesis
Charalampia Koutsioumpa1, Celine Santiago2, Kiani Jacobs2, David Ginty2
1Yale University, 2Harvard Medical School
Objective:
Identification of the mechanisms of sensory neuron morphogenesis.
Background:

We use our sense of touch in order to detect and manipulate objects, socially interact, and tell apart harmful from nonharmful stimuli on the body. Sensory neurons detect our environment through their projections to the skin. However, sensory neuron endings are strikingly different depending on the skin type they innervate – hairy or hairless (glabrous) skin. How sensory neuron endings develop their morphological and functional properties in order to match the skin type they innervate remains unknown. Bone morphogenetic proteins have been previously shown to be critical for development of glabrous (hairless) skin. Since sensory neurons and skin develop in parallel, we hypothesized that BMP signaling acts on sensory neurons to specify aspects of their morphogenesis.

Design/Methods:

To examine the developmental dynamics of BMP expression in mouse glabrous and hairy paw skin, we used in situ hybridization (RNAscope) to localize mRNA transcripts of different members of the BMP ligand family. Additionally, to selectively ablate BMP signaling through BMP type I receptors, we generated mice which have the Bmpr1a and/or Acvr1 receptor genes deleted in all somatosensory neurons beginning at embryonic day 12.5. We performed anatomical studies to examine the effects of the deletion on somatosensory neurons.

Results:
We find that different members of the BMP family, in particular BMP5 and BMP7 are enriched in the glabrous skin at developmentally critical time points. On the contrary, inhibitors of BMP signaling are enriched in hairy skin. We also show that a bone morphogenetic protein (BMP) type I receptor signaling pathway is critical for shaping the architecture of glabrous skin specific end organs, and not for hairy skin morphogenesis. 
Conclusions:
Our findings support a model in which cues from the skin instruct sensory neuron morphogenesis and thus their unique physiological roles.
10.1212/WNL.0000000000205522