Greg Barsh, MD, PhD / Barsh Lab
Morphological variation in mammalian color patterns
Zebras, tigers, and cheetahs are all instantly recogniz- able because of their fur patterns and markings. These distinctive patterns serve to camouflage the animals from predators and to help them identify others belong- ing to the same species. The study of the color, structure and form of living animals, called morphology, is a fun- damental aspect of biology. Morphology provides a basis for the understanding of function, development, heredi- ty, taxonomy, ecology and other branches of biology. HudsonAlpha Faculty Investigator Greg Barsh, MD, PhD, is an expert in the genetics of morphological varia- tion, both within and between species. Barsh uses color and color pattern as an experimental platform to study cellular and molecular pathways that are used through- out the body. One goal of the Barsh lab is to understand the development and evolution of periodic color pattern in mammals, to better understand the molecular toolkit that biology uses to generate form and function. Domestic cats are a useful model to study peri- odic color patterns, especially tabby cats whose hair color pattern and form varieties are similar to wild cat species. Barsh and his group previously showed that a gene called Endothelin 3 is expressed at the base of hair follicles in tabby cat markings and plays a key role in the development of tabby pattern 1 . However, tabby markings are apparent in developing hair follicles, indicating that establishment of color pattern must occur at or before hair follicle development. In a new study available on bioRxiv , the group determined when, where, and how, cat color patterns are established during fetal development 2 . Histochem- ical analysis of fetal cat skin revealed stripe-like alter- ations in skin thickness early in fetal development. The skin thickness resembled tabby fur patterns in adult animals. This finding suggests that even before mela- nin-producing cells, called melanocytes, enter the skin, the cells are predestined to signal for a specific fur color. By using single-cell gene expression analysis on fetal cat skin cells, they determined that skin cell expression of a gene called Dickkopf 4 ( Dkk4 ) marks areas of fetal skin that give rise to hair follicles that later
produce dark pigment. Dkk4 -expressing skin cells acquire time-sensitive epigenetic changes that are lat- er incorporated into hair follicles, and ultimately deter- mine whether the underlying skin cells release mole- cules that darken or lighten the hair. The team also showed that two variants in Dkk4 are linked to another genetic locus involved in color pattern- ing, called Ticked . Ticked prevents dark tabby markings, producing hair banding patterns across the entire body surface. Taken together, the results presented in this study confirm a direct role for Dkk4 in cat color pattern establishment, providing a new target for periodic color variation in other mammals. Cats are not the only domesticated animal species with a range of diverse looking members—dogs also have a wide variety of fur colors and color patterns. Barsh is also interested in discovering the genetic basis of coat color in dogs. In a preprint publication avail- able on bioRxiv , Barsh and his colleagues explored the genetic control of pigmentation in dogs, specifically why so many domesticated dogs are yellow, and what genet- ically differentiates a yellow dog from a black dog 3 .
Cat skin histology showing black and yellow hair follicles
HudsonAlpha Institute for Biotechnology
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