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Tension on skin sets up evenly spaced cell clumps, turning on genes that produce follicles & feathers https://www.eurekalert.org/pub_releases/2017-07/uoc--mcf071817.php
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How to make chicken feathers

It appears skin tension sets up the conditions for activating genes to produce follicles and feathers. The rubber-like elasticity of skin which makes it contract to its original shape after stretching, is key to forming hair or sweat glands during development, or can turn follicles into feathers based on the tension of the skin.

The findings come from experiments on how chicken skin generates feathers as an embryo inside the egg. The discovery could provide tips for scientists on how to grow artificial skin for grafts, complete with hair follicles and sweat pores. Just the right tension on growing skin could set up these organized structures without the need of chemicals to trigger their formation.
The research is the first linking the normal tug of war between cells as an organism grows, with activating genes that make cells differentiate into unique cell types such as turning a generic skin cell into a specialized follicle cell that gives rise to a feather.

"The cells of the skin in the embryo are pulling on each other and eventually pull one another into little piles that each become a follicle," explains embryologist Amy Shyer, a Miller postdoctoral fellow in the UC Berkeley Department of Molecular and Cell Biology. "What is really key is that there isn't a particular genetic program that sets up this pattern. All of these cells are initially the same and they have the same genetic program, but their mechanical behavior produces a difference in the piled-up cells that flips a switch, forming a pattern of follicles in the skin."

These characteristics of "tension" over genetics, may be seen as an epigenetic influence, or an external influence not associated with any genetic programming.

Amy Shyer along with Alan Rodrigues, an independent biologist and former UC Berkeley visiting scholar, are first authors of the paper announcing these findings published online July 13 by the journal Science.
The research connects two schools of thought about how the intricate complexity of an organism arises. One being the complete body plan of an organism as determined by a genetic program beginning at conception, which dictates each cell's destiny. Another, older idea is that interactions among cells, together with the influences of things they grow on or near, are key in determining cell fate.

Rodrigues: "One of our key assertions is that the specification of this pattern is not directly encoded in the genome. There is no enhancer saying, 'you' are going to become a follicle, but 'you' are not. Which is how a lot of people often think about this." Enhancers are short stretches of DNA upstream of a gene that regulate that gene's expression/function.

Shyer and Rodrigues tested different types of materials on which to grow skin taken from week-old chicken fetuses. Artificially created substrates mimiced the stiffness of tissues underlying a bird's skin. Skin slices were transferred to an artificial substrate and pulled tightly against it. Pulling tended to evenly space spots throughout the skin, squeezing adjacent cells in the overlying epidermis to activate genes and produce feather follicles. However, if the substrate material was too stiff or too soft, dermal cells clumped together into one large follicle producing one feather. This result might explain why feathers are differently spaced on different parts of a bird.

Chick embryos are analogous in age to about one month gestational humans, a point at which the human embryo looks similar to other fetal vertebrates. This is also the stage when a rough outline begins for each internal organ. Carnegie Stage 13

"This suggests that the principles we've uncovered at this particular stage are highly conserved across all animals, and could be a basic [developmental] mechanism."

Alan R. Rodriques PhD, Department of Molecular and Cell Biology, University of California, Berkeley,CA, and Department of Genetics, Harvard Medical School, Boston, MA, USA.
The research also revealed that squeezing epidermal cells triggered a protein known as beta-catenin which normally sits on the surface of the epidermal cell regulating cell adhesion, to relocate into the nucleus. This relocation flips a switch initiating a genetic program to differentiate each clump of cells into a feather follicle.

Rodrigues: "We have gotten really good at taking stem cells and making them progress into different fates. But we are not good at controlling, in a clean way, how those cells organize into unique structures as they differentiate. Figuring out how to achieve the right fate and right architecture at the same time is something that embryos have already solved."

The spacing of hair in mammals and feathers in birds is one of the most apparent morphological features of the skin. This pattern arises when uniform fields of progenitor cells diversify their molecular fate while adopting higher-order structure. Using the nascent skin of the developing chicken embryo as a model system, we find that morphological and molecular symmetries are simultaneously broken by an emergent process of cellular self-organization. The key initiators of heterogeneity are dermal progenitors, which spontaneously aggregate through contractility-driven cellular pulling. Concurrently, this dermal cell aggregation triggers the mechanosensitive activation of ?-catenin in adjacent epidermal cells, initiating the follicle gene expression program. Taken together, this mechanism provides a means of integrating mechanical and molecular perspectives of organ formation.

All authors: Amy E. Shyer, Alan R. Rodrigues, Grant G. Schroeder, Elena Kassianidou, Sanjay Kumar, and Richard M. Harland, Professor, Molecular and Cell Biology in whose lab Shyer and Rodrigues initiated this study.

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Jul 28, 2017   Fetal Timeline   Maternal Timeline   News   News Archive

In this cross-section through chicken skin, the dermal cells are green, overlain by the purple epidermal layer at the top. The embryonic tissue to which these cells attach is at the bottom.
Image credit: Amy Shyer, UC Berkeley

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