Basic Mechanisms in the Differentiation of
Pigment Cells
by B. H. WILLIE R1
The Johns Hopkins University
of the basic mechanisms of cellular differentiation have been elucidated
by an experimental analysis of the underlying factors and conditions which
control the processes of differentiation of the pigment cell in the chick embryo.
The pigment cell, owing to its singular capacity to synthesize melanin pigment
granules, is an ideal cell for locating its site of origin and tracing its subsequent
pathways to the skin and derivatives, the feather papillae. It has the further advantage that its specific behaviour is recorded as colour or colour pattern in the
mature feather. In other words, by using the pigment-forming cell as a 'marker'
many of its properties in time and space may be ascertained from the moment
that it is first set aside as a specialized strain of cell until it reaches its ultimate
position and visible expression in the growing feather papilla.
1. In the chick the pigment-forming cell is a specialized strain of cell which
has been traced back to early phases of development, i.e. ultimately and exclusively to the neural crest. Just when and by what means it acquires the basic
properties and mechanisms which distinguish it from other cell types is not
known. The evidence, however, indicates that the pigment-forming cells are
intrinsically different from the beginning of the experimental test. At least some
of the neural crest cells already have or soon acquire the latent capacity to synthesize melanin pigment granules, from which time they are appropriately designated as melanoblasts. Sooner or later these cells when associated with a suitable
tissue environment begin the synthesis of melanin granules, from which time
they are designated melanophores.
Once endowed with properties peculiar to their kind, i.e. the combined
capacity for migration and the synthesis of melanin pigment granules, the
melanoblasts migrate from one position to another in a dorso-ventral direction
apparently in strict conformity with the specific properties of the tissue substratum prevailing at the time along their pathways. In other words, the melanoblasts appear to be 'guided' by the specific and oriented conditions prevailing
in the dermal tissue immediately subjacent to the skin ectoderm and in certain
other tissues as well. In this manner the melanoblasts within the skin migrate to
SOME
1
Author's address: Department of Biology, The Johns Hopkins University, Charles and
Strs., Baltimore 18, Md., U.S.A.
[J. Embryol. exp. Morph. Vol. 1, Part 3, pp. 297-299, September 1953]
298
B. H. WILLIER—DIFFERENTIATION OF PIGMENT CELLS
each of the developing feather papillae, at or near the base of which they become
permanently established, thereafter constituting a constant source of melanoblasts to the feather throughout the life of the bird (Willier, 1948).
While in the relatively undifferentiated state, the melanoblasts have the capacity for growth (often increasing markedly in number), apparently by synthesizing more of the basic protoplasm capable of melanin synthesis (ordinarily
melanin granules are not formed until after growth ceases). The melanoblasts
may, therefore, be regarded in a sense as self-reproducing systems capable of
growing indefinitely. The number of melanoblasts at a given stage and locus,
however, is controlled not by a self-limitation of capacity for multiplication but
by the tissue community in which they reside (Willier, 1948).
By virtue of specialized properties acquired during the earlier phases of differentiation the melanoblasts can combine, interact, and arrange themselves in
certain specific and orderly ways relative to the developing epidermal tissue
elements of the feather papilla. As an orderly morphogenetic system the feather
papilla governs in sequence (1) the time of invasion of the melanoblasts, (2) their
rate of multiplication and spatial arrangement in the developing epidermal elements of the feather, and likewise (3) the exact time and locus of transformation
of a melanoblast into a melanophore with accompanying synthesis of melanin
pigment granules. Further, it seemingly regulates (4) the order and direction of
dendritic outgrowths from the melanophore as well as (5) the time that melanin
granules are discharged and accepted by the epidermal cells. All processes of
interaction between melanoblasts and the epidermal components are closely
correlated in time (Willier, 1942, 1952).
2. Although the developing feather papilla clearly acts upon the melanoblasts
in guiding their orderly behaviour and response, the specific kind of colour
reaction given by the melanoblasts is basically dependent upon their specific
genetic constitution. Invariably the kind of colour response is determined by the
specific assemblage of colour or pattern-producing genes within them. In this
respect the melanoblasts of the various breeds of fowl exhibit a wide diversity
ranging from a lethal type (foreshortened life span resulting in white plumage)
to a type capable of producing an intricate, sexually dimorphic colour pattern in
the feather. Furthermore, melanoblasts of the colour-pattern genotype exhibit
differences among themselves in reaction to sex hormones, some being sensitive
whereas others are insensitive. The reaction of the hormone-sensitive melanoblast is looked upon as a matter of adjustment to the changes brought about in
the feather papilla by the action of sex hormones. It is the harmonious organization of the feather papilla that integrates and utilizes sex hormones in directing
the course of differentiation of the hormone-sensitive melanoblasts. The effect of
the hormonal stimulus is indirect; it is mediated through the epidermal system of
the feather papilla (Willier, 1950).
Finally, it is to be noted that all melanoblasts, irrespective of their genetic constitution, have in common certain basic properties such as the capacity to respond
B. H. WILLIER—DIFFERENTIATION OF PIGMENT CELLS
299
in an orderly manner to organized tissue environment and for the synthesis of
melanin from precursor substances. So far as the underlying biochemical processes are concerned, little information is available save that tyrosinase or allied
enzymes are in all probability localized in the melanoblasts. However, with
EPIDERMAL
SUBSTRATUM
MELANOBLAST
.MELANOPHORE
IPRODUCT)
HORMONAL MODIFICATION OF GENE-CONTROLLED PROCESSES
IN MELANOBLAST DIFFERENTIATION
respect to the terminal products in the differentiation process, the specific colourproducing genes have a decisive role in determining the range of reaction of
which the melanoblast is capable. The range may be limited (self colour) or manifold (colour pattern). In the case of the hormone-sensitive melanoblast of the
colour-pattern genotype, a change in the synthetic processes takes place in response to the action of the sex hormone. The sex hormones somehow affect one
or more steps in the chain of biochemical processes involved in the synthesis of
melanin, such that melanin granules which differ in morphology (size and shape),
in colour, and presumably in chemical composition are produced (see Fig.).
REFERENCES
Citations to the original literature and the detailed evidence on which this article is based are
given in the review papers listed below.
WILLIER, B. H. (1942). Hormonal control of embryonic differentiation in birds. Cold Spr. Harb.
Symp. quant. Biol. 10,135-44.
(1948). Hormonal regulation of feather pigmentation in the fowl. The Biology of Melanomas. Special Pub. N. Y. Acad. Sci. 4, 321-40.
(1950). Specializations in the response of pigment cells to sex hormones as exemplified in the
fowl. Arch. Anat. micr. 39, 451-66.
(1952). Cells, feathers and colors. Bios, 23, 109-25.