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  • Cell lineage: The family tree history of a cell through all of its divisions.

  • Clone: Any distinct cell and all of its progeny.

  • Differentiation: The process where a cell becomes increasingly specialized in their cellular lineage. The least-differentiated cells are the totipotent embryonic stem cells which can develop into any cell in the body. The most differentiated cells are restricted to their type and have the least potential to become another type of cell. The differentiation status of a cell is usually firm, and in most cases thought to be irreversible. This chapter essentially discusses how the least-differentiated cells eventually form skin and become differentiated to the terminal cells of a mature organism.

  • Dedifferentiation: The process where a cell might reverse its otherwise fixed differentiation status.

  • Epithelial–Mesenchymal Interactions: This describes the crosstalk between keratinocytes and fibroblast during morphogenesis.

  • Regenerative Medicine: The field whose goal is to harness the concepts of developmental biology for dedifferentiation of adult tissues and allow reactivation of embryonic programs for the recreation of lost structures.

  • Chimerism or Mosaicism: During development, the emergence of genetic mutations in an otherwise normal animal which create distinct lineages of mutant cells or clones.

  • Blaschko Lines: The migration pattern of skin cells during embryonic development can be visualized in adults if that individual is a chimera and a distinct clone has a clinical abnormality such that it is visible in the background of other skin cells. This is most obvious with the keratinocyte mutations that occur in utero during skin morphogenesis such that they are intermixed with normal cells.



  • The skin is divided into 3 layers:

    • Epidermis: Forms the barrier to outside world and is the locus of immune surveillance and activation to prevent and combat infections.

    • Dermis: Provides the main structural substance (collagen) of skin. Forms a main interface to vasculature and nervous system in the skin, and intimately interfaces with epidermis to coordinate skin function.

    • Hypodermis: The area beneath the collagen-rich dermis that is characterized by subcutaneous adipose tissue with a role in energy balance, as well as recently defined roles in epidermis crosstalk and immune surveillance.

  • Skin development, as for other organs, occurs in the stepwise progression from more pluripotent to increasingly differentiated cells with specialized function.

How does your entire body form from a single cell? The process of development is perhaps one of the most complicated events in biology, yet occurs with startling fidelity. This chapter discusses how the skin develops as a means to introduce the reader to the structures of the skin; to create a framework to understand normal skin function; and to learn how its normal development is disrupted in a variety of inherited genetic diseases that manifest with skin symptoms.

As science and medicine increasingly converge, knowledge of normal skin development is increasingly important. For example, knowing the normal function of skin structure allows the clinician greater ...

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