WNT and DKK Determine Hair Follicle Spacing Through a Reaction-Diffusion Mechanism

Abstract

Mathematical reaction-diffusion models have been suggested to describe formation of animal pigmentation patterns and distribution of epidermal appendages. However, the crucial signals and in vivo mechanisms are still elusive. Here we identify WNT and its inhibitor DKK as primary determinants of murine hair follicle spacing, using a combined experimental and computational modeling approach. Transgenic DKK overexpression reduces overall appendage density. Moderate suppression of endogenous WNT signaling forces follicles to form clusters during an otherwise normal morphogenetic program. These results confirm predictions of a WNT/DKK-specific mathematical model and provide in vivo corroboration of the reaction-diffusion mechanism for epidermal appendage formation.

Visible-to-Near IR Quantum Dot–Based Hypermulticolor High-Content Screening of Herbal Medicines for the Efficacy Monitoring of Hair Growth Promotion and Hair Loss Inhibition

“…Compared with Wnt5α, DKK-1 also affects Wnt signaling, with the opposite effects on hair growth. 21 DKK-1 as a Wnt antagonist binds to Wnt coreceptors of the LRP family and suppresses the canonical Wnt signaling pathway. Therefore, the growth of ORS cells is inhibited by DKK-1, and balding dermal papilla cells (DPC) are activated.…”

Mimicking nature by codelivery of stimulant and inhibitor to create temporally stable and spatially restricted angiogenic zones

“…This methodology mimics developmental processes in nature that use opposing factors as a method of control. Reaction-diffusion mechanisms involving an inhibitor and an activator manifest in murine interfollicular patterns, angelfish skin patterns, and avian feather size and spacing (35)(36)(37). The polymer system described in the present paper is also robust against fluctuations in angiogenic VEGF threshold and initial encapsulated mass.…”

Stability analysis of non-autonomous reaction-diffusion systems: the effects of growing domains

“…Turing patterns were first observed by Castets et al (1990) in a chloride-ionic-malonic-acid (CIMA) reaction and Ouyang and Swinney (1991) were the first to observe a Turing instability from a spatially uniform state to a patterned state. Although controversial in a biological context for many years, recent experimental findings suggest this may be a mechanism for the formation of repeated structures in skin organ formation (Sick et al 2006;Maini et al 2006) and zebrafish mesoderm cell fates (Solnica-Krezel 2003).…”