Johns Hopkins Scientists Build a 4D Map of How Hair Follicles Form

Scientists at Johns Hopkins Medicine say they have developed a new imaging technology that captures a 3D molecular 'snapshot' of hundreds of developing hair follicles and reconstructs a fourth dimension — time — to build a stop-motion animation of how the organ forms, according to a study published in the journal Cell.

The tool, called 3D DNase-Enhanced Expression Profiling (3DEEP), removes genomic DNA that would otherwise interfere with visualizing messenger RNA (mRNA, a molecule that carries a gene's instructions for building proteins), then labels the positions of millions of RNA molecules to build a precise 3D map of gene activity in a tissue sample. The researchers used it on skin from normal mice and from hairless mice lacking a gene called Foxn1, which is critical for hair growth.

Analyzing this 4D map, the researchers identified distinct phases of follicle formation: precursor cells first organize in space to establish the organ's axis perpendicular to the skin surface, then differentiate into the various cell types needed, before those cells grow and mature into a follicle ready to produce a hair strand.

Comparing normal and hairless mice, the team found follicles in the Foxn1-deficient mice developed on a delayed schedule — their cells divided faster but were less able to mature and take on specific roles at the right time, and the follicles structurally collapsed before hair could form.