1. Skin Pigmentation:
Cell Biology
slide version 1.0

2. Skin Pigmentation Introduction
Learners will be able to:
Summarize the roles of gene expression and natural selection in “building” an organism.
Describe basic functions of the skin.
Explain the function of melanocytes, melanosomes and keratinocytes.
Model the relationship between melanocytes and keratinocytes.

3. Introduction: Building Organisms
It takes thousands and thousands of proteins to build an organism from a fertilized egg to an adult. These proteins exist in cells of organisms because of two fundamental biological processes: Gene Expression and Natural Selection

4. Gene Expression
Some genes are expressed (the proteins for which they code are made) only during development in all or a subset of cells.
Some genes are expressed in adults in all or a subset of cells.
In any cell at any given time hundreds of gene products, proteins, are interacting to make a cell tick.
Adding to this complexity is the fact that there may be several alternative forms of a gene leading to protein variations.

5. Multiple Gene Expression Human Skin Color
We often hear of a “gene for” a given characteristic. There are a few examples of a trait being associated with a particular configuration of alleles for a particular gene.
However, most characteristics, as is the case for skin color, are the result of the expression of tens, if not hundreds, of genes.
These proteins, expressed during both development and maintenance of mature skin cells, lead to skin with a unique color.
We follow the convention that “characteristic” is the phenotype and a “trait” is a variation of that phenotype. Skin color is the characteristic. Brown skin is the trait.

6. Natural Selection
The world is fraught for an organism from fertilization to age of reproduction. Literal and figurative tigers, and lions and bears (oh my!) are abundant. The weather is variable. Your stream may become polluted. The volcano on which you live may blow up. Your skin may fry. There is no shortage of ways for a juvenile organism to die. And then: those making it to adulthood may not reproduce as much as other adults in the neighborhood. Or maybe not at all.

7. Natural Selection Differential Reproduction
BUT if you make it, the payoff is huge – you get to reproduce! Yes! You win! And the more babies the better! And the more of your babies that are able to reproduce big time, the more your (and your mate’s) genes will be carried forward into grandchildren, great-grandchildren, great-great-grandchildren (you get the idea).
Image from pixabay.com

8. Cell Biology of Skin

9. How do cells “color” skin?
Skin color varies widely among and between populations. We can observe among our friends and acquaintances that there are gradations in skin color. We also have a pretty good sense that skin color of indigenous populations is correlated with where they are on Earth. How do cells “color” skin?
Image from Sturm, Molecular genetics of human pigmentation diversity. Hum Mol Genet. 2009;18(R1):R9-R17. doi: /hmg/ddp003

10. Functions of Skin I
We don’t always think of skin as an organ, but it is the largest one we have.
One function is to act as a barrier between our outside and inside worlds.
Sometimes we break our skin. When that happens our inside world, usually blood, goes outside and the outside world, usually bacteria, can go in.
Most often, these breaks heal without huge consequences.

11. Functions of Skin II
Skin also has sensors that allow us to respond to our environment.
Skin-to-skin contact is very important in making human connections and for the development of babies.
Photo: M. Heidemann

12. Functions of Skin III
Our skin is also host to a thriving ecosystem of microbes, part of the human microbiome. They help control the “bad guys” living on our skin.
Image from pixabay.com

13. Functions of Skin IV
Finally, skin interacts with the sun’s UV radiation. Sometimes this interaction is good; sometimes it’s bad. A lot depends on where on Earth you live.
Sun from openclipart.org

14. Structure of Skin
Human skin has three basic layers (from outside to inside): the epidermis, the dermis and the hypodermis.
Since skin color is expressed in the epidermis, we will focus our discussion on cells of that layer.
Photo from pixabay.com

15. Cell Biology of Epidermis
The epidermis consists of two kinds of cells: Keratinocytes that migrate upward, forming the outermost layer. These eventually die and slough off. The color of skin depends on pigment packages, melanosomes, in these cells. Melanocytes that produce the pigment melanin (there are two major kinds) in packages, melanosomes, which are transferred to the keratinocytes.

16. Keratinocytes and Melanocytes Key Features
Melanocytes (brown) make and transport melanosomes for several “client” keratinocytes. They have long skinny “arms” to accomplish this. The Keratinocytes (pink) have variable numbers and sizes of melanosomes (black) that cluster around the nucleus,
Image:
Blue = cell nuclei.

17. Melanosomes
Melanosomes begin life as a membrane “bag”. Over time, as pigment synthesis continues, melanosomes becomes darker and darker as they migrate to the edge of the melanocyte. Left: diagram of melanosome formation Right: electron micrograph of maturing melanosomes
Figure from Marks and Seabra, Nat Rev Mol Cell Bio 2:

18. What Do Melanosomes Do?
This electron microscope image shows melanosomes clustering near the nucleus of keratinocytes. They protect it from damaging ultraviolet rays by absorbing this relatively high energy light. Dark skin has more and larger melanosomes around the nucleus of keratinocytes that does light skin.
Image from. J dermatol 149(3): , 2003.

19. Keratinocytes and Melanocytes
Each melanocyte makes and transports pigment-containing melanosomes to 36 – 40 keratinocytes. Data suggest that melanosomes are passed off to keratinocytes by one of two mechanisms (see next slide):
melanocytes shed membrane bound packages of melanosomes, which the keratinocytes take up (phagocytosis); OR
melanocytes “eject” individual melanosomes, which are taken up by keratinocytes (endocytosis).

20. Passing off Melanosomes from Melanocytes to Keratinocytes
Diagram modified from Wu and Hammer Current Opinion in Cell Biology 29:1–7

21. Keratinocytes and Melanocytes Cross Talk
This is cool: melanosome synthesis is stimulated by messages to melanocytes from the keratinocytes themselves. This is a special kind of messaging, called paracrine signaling, that happens between neighboring cells. This is especially important in the tanning process and helps to protect the nucleus of keratinocytes from UV radiation damage.
Image from openclipart.org