Using naturally evolved phenotypic variation to decipher the positional regulatory code of mammalian skin

Princeton University, Princeton NJ

Investigators

Linked publications & trials

Abstract

PROJECT SUMMARY Changes occurring during embryogenesis are typically lethal or can lead to congenital malformations. In many cases, however, these changes can be beneficial because they can promote the origin of new traits and the evolution of adaptations. Because of this relationship between deleterious and viable variation, studying naturally occurring phenotypic diversity across the animal kingdom provides a powerful framework to study a fundamental question in developmental biology and biomedical sciences: How can development change without detrimental consequences? Our laboratory harnesses natural variation in mammalian skin to understand how changes during development can generate phenotypic variation. Through work funded by my Early-Stage Investigator R35, we have studied two distinct spatially patterned phenomena during skin development: (1) Stripe pattern formation in rodents, and (2) Gliding membrane formation in marsupials. As proven by our track record, this work has significantly advanced our understanding of the mechanisms by which skin is patterned. In the new funding period, we will focus on studying stripe pattern formation in rodents to uncover the mechanisms by which skin can acquire positional information and how such mechanisms have been modified across evolutionary time to produce different phenotypic outcomes. To achieve this, we will build on our solid findings from previous studies, on our exciting new preliminary data, and on the wide array of genomic and molecular tools that my laboratory has already developed. First, using the African striped mouse as a model, we will investigate the mechanisms by which pigment patterns are established and implemented. Specifically, we will uncover how a Wnt signaling gradient in the dorsal skin is established; how spatiotemporal dynamic patterns of gene expression are achieved, and what is the contribution of different hair follicle cell types to modulating differences in coat color. Then, using a comparative approach, we will study how pigment patterns can diverge. In particular, we will study how differences in placode patterning across species are established and we will uncover the regulatory mechanisms by which spatial differences in pigmentation gene expression can be achieved. The approaches described in this research program integrate multiple disciplines, including developmental biology, functional genomics, and computational biology, with my lab’s expertise in skin developmental biology and demonstrated success developing molecular tools in emerging model species.