Pigment Cell Growth. Proceedings of the Third Conference on the Biology of Normal and Atypical Pigment Cell Growth

373 Pages·1953·8.417 MB·English

by  Myron Gordon (Eds.)

Pigment Cell Growth
Proceedings of the Third Conference
on the
Biology of Normal and Atypical
Pigment Cell Growth
Edited by
MYRON GORDON
New York Zoological Society, New York
1953
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Copyright 1953, by
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LIST OF AUTHORS
GLENN H. ALGIRE, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland
BELLE F. ANDERSON, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland
ALICE S. BAKER, Department of Chemistry, The Florida State University,
Tallahassee, Florida
S. WILLIAM BECKER, University of Chicago School of Medicine, Chicago,
Illinois
OLGA BERG, New York University and New York Zoological Society, New
York, Neiv York
DEAN BURK, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland
CHARLES CHESNER, Western Reserve University, Cleveland, Ohio, and St.
Joseph Hospital, Lorain, Ohio
RANDOLPH LEE CLARK, JR., M. D. Anderson Hospital for Cancer Research,
Houston, Texas
HELEN OLLENDORFF CURTH, Department of Dermatology, College of Physi-
cians and Surgeons, Columbia University, New York, New York
ALBERT J. DALTON, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland
H. CLARK DALTON, Department of Biology, Washington Square College of
Arts and Science, New York University, New York, New York
H. G. DU BUY, Microbiological Institute, National Institutes of Health,
Bethesda, Maryland
EDWARD A. EDWARDS, Department of Anatomy, Harvard Medical School,
and the Department of Surgery, Peter Bent Brigham Hospital, Boston,
Massachusetts
MARIE D. FELIX, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland
THOMAS B. FITZPATRICK, Department of Dermatology, University of Oregon
Medical School, Portland, Oregon
DAVID M. GERBER, Memorial Center for Cancer and Allied Diseases, New
York, New York
MYRON GORDON, Genetics Laboratory, New York Zoological Society, and
New York University, New York, New York
MARIE HESSELBACH, Microbiological Institute, National Institutes of Health,
Bethesda, Maryland
GEORGE HOBBY, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland
F. B. HUTT, Department of Poultry Husbandry Cornell University, Ithaca,
f
New York
AUTHORS
M. J. KOPAC, Department of Biology, Washington Square College of Arts
and Science, New York University, New York, New York
FRANCES Y. LEGALLAIS, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland
AARON BUN SEN LERNER, Department of Dermatology, University of Oregon
Medical School, Portland, Oregon
PROSPER LOUSTALOT, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland
HERBERT Z. LUND, Institute of Pathology, Western Reserve University,
Cleveland, Ohio, and St. Joseph Hospital, Lorain, Ohio
ELEANOR J. MACDONALD, M. D. Anderson Hospital for Cancer Research,
Houston, Texas
H. S. MASON, Departments of Biochemistry and Dermatology, University
of Oregon Medical School, Portland, Oregon
GEORGE T. PACK, Memorial Center for Cancer and Allied Diseases, New
York, New York
JEWEL I. PLUMMER, Department of Biology, Washington Square College of
Arts and Science, New York University, New York, New York
RONALD W. RAVEN, The Royal Cancer Hospital and Westminster (Gordon)
Hospital, London, England
MARY E. RAWLES, Department of Biology, The Johns Hopkins University,
Baltimore, Maryland
VERNON RILEY, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland
ISABEL M. SCHARNAGEL, Memorial Center for Cancer and Allied Diseases,
New York, New York
JANE L. SHOWACRE, Microbiological Institute, National Institutes of Health,
Bethesda, Maryland
HERBERT J. SPOOR, New York Medical College, New York, New York
EUGENE F. TRAUB, New York Medical College, New York, New York
J. P. TRINKAUS, Osborn Zoological Laboratory, Yale University, New Haven,
Connecticut
M. W. WOODS, Microbiological Institute, National Institutes of Health,
Bethesda, Maryland
PREFACE
Conferences on the Biology of Normal and Atypical Pigment Cell Growth
were organized to meet the needs of biologists, chemists, physicists, statis-
ticians and medical research workers who are studying various aspects of this
common problem. The meetings were designed to offer each specialist an
opportunity to explore paths of inquiry other than his own. The program
was arranged so that the nature of the pigment cell and its contained
melanin would be described, possibly explained, and certainly discussed. The
sessions were so planned that each member could evaluate, compare and
integrate the speakers' experiences, results and conclusions with his own
experiences and convictions. It is becoming evident that an understanding
of atypical growth, whether of pigment cells or of any other cells, will be
achieved most probably from a synthesis of knowledge from many research
fields, not from one alone.
The crossfire of facts and interpretations exchanged between members
representing allied disciplines, and those exchanged between representatives
from entirely different fields, produced information for everyone, some agree-
ment, but principally an awareness of the magnitude of the problem. Its
urgency was revealed to all by dermatologists, pathologists, and surgeons
who see, study, and carry out the recommended procedures in the treatment
of the melanoma patient. The malignant potentialities of melanocytes are
great. What makes them so may be understood after we know where they
originate, along what route they migrate and, most important, what factors
control their normal or atypical growth.
The papers presented at this conference may be compared with those
given five years ago and published in "The Biology of Melanomas." While
some papers in the present volume reemphasize the basic problems, others
open new channels of thought and methods of dealing with pigment cell
growth. Only this is certain and predictable: when sufficient fundamental
information concerning the nature, development and growth of pigment cells
is within our grasp, then a means of controlling the melanoma will follow.
The Conferences on Pigment Cell Growth will continue in the future at two
to three year intervals. They have provided the most practical method of
bringing the new information to a common center for friendly and frank
discussions. As always, the organizing chairman welcomes suggestions for
titles of papers that will describe new aspects of the subject. Anyone who
wishes to be kept informed of future meetings of the Pigment Cell Growth
group has but to write to the chairmen, authors or discussants indicated in
this volume. The only requirement for attendance or participation is an
interest in the history of the pigment cell and in its growth.
PREFACE
PIGMENT CELL TERMINOLOGY
Ordinarily in a volume of this kind, which represents cooperative en-
deavor, the organizing chairman confines his preface briefly to its history
and objectives. But an extraordinary event happened at the close of the
Third Conference, and I have been asked to report it here.
During the conference many speakers found it necessary to define their
terms when referring to the pigment-bearing cells because definitions for
the same word varied. For example, biologists in general used the word
"melanophore" in referring to melanin-containing stellate cells which are
responsible for color changes in reptiles, amphibians, fishes, and some inver-
tebrates. A melanophore, thus, is a cell in which coloring matter may be
either dispersed throughout the cell or concentrated in its center, depending
upon the physiological state of the animal. This conforms to the use of the
original Italian term cratnoforo, which was coined by Sangiovanni in 1819.
Some medical workers had been following Bloch, who used the term "melano-
phore" to denote a melanin-bearing macrophage. While the term melano-
phore when literally translated means a melanin-carrying cell, biologists
pointed out that this word had come to denote a special kind of pigment-
carrying cell, one that is quite different from the macrophage.
Because of confusion in terminology, it was decided to hold a post-
conference session in an attempt to adopt a uniform nomenclature. The
group unanimously recommended the following terms and definitions:
Melanoblast: an embryonic cell potentially capable of producing
melanin.
Melanocyte: a mature melanin-producing and melanin-containing
cell.
Macrophage: a cell containing phagocytized melanin.
Melanophore: a pigment effector cell in lower animals.
The recommended terms were submitted by one of our conferees to the
Subcommittee on Oncology within the Division of Medical Sciences of the
National Research Council. The terms and definitions were sent to authors
preparing fascicles for their comprehensive Atlas of Pathology. It is par-
ticularly gratifying that the forthcoming fascicle on "Melanotic Tumors of
the Skin" will adopt the terms suggested by our group.
ACKNOWLEDGMENTS
The papers and discussions in this volume were presented at the Third
Conference on the Biology of Normal and Atypical Pigment Cell Growth
held at the New York Zoological Park, Bronx, New York, on November 15,
16 and 17, 1951, under the sponsorship of the New York Zoological Society.
PREFACE
Dr. Ralph G. Meader was the chairman of the first session. He opened
the meetings by introducing Mr. Fairfield Osborn, President of the New
York Zoological Society, who welcomed the members to the conference.
During the first morning, papers were read on the embryological and genetic
aspects of the subject. In the afternoon, papers covering the endocrino-
logical and pathological phases of the problem were presented. The second
day's papers, under the chairmanship of Dr. H. W. Chalkley, were devoted,
during the morning, to methods of study and treatment of normal and
abnormal pigment cell growth in man. The afternoon session took up the
physiological, particularly the enzymatic problems of melanogenesis. The
third day's presentations, under the chairmanship of Dr. Dean Burk, dis-
cussed the chemical and physical nature and activity of melanin-containing
cells.
The Organizing Chairman takes this opportunity of thanking all the
participants of the Third Conference for their splendid efforts which have
made this volume possible. This conference, like the first and second, was
encouraged by a grant from the Anna Fuller Fund upon the recommenda-
tion of its Medical Advisor, Dr. George Milton Smith. It is with deep sorrow
that I report the death of Dr. Smith, on February 26, 1951. His thoughtful
suggestions inspired the formation of these Conferences, and his practical
approach to their needs provided funds to implement them. Additional funds
to meet the expenses of the Third Conference were made available by the
New York Zoological Society.
The publication of this volume was aided greatly by a generous grant
from the Damon Runyon Memorial Fund, for which we express our thanks.
MYRON GORDON, Organizing Chairman.
Genetics Laboratory of the New York Zoological Society at the
American Museum of Natural History, New York 24, New York.
Origin of the Mammalian Pigment Cell and Its Role in the
Pigmentation of Hair*
BY MARY E. RAWLES
Department of Biology, The Johns Hopkins University, Baltimore, Maryland
CONTENTS
Page
I. Introduction 1
II. Source of Pigment Cells in the Embryo 1
III. Migration of Precursor Pigment Cells (Melanoblasts) into the Skin . 6
IV. Pigment Cells Essential for Pigmentation of Hair 8
V. Conclusion 12
References 12
I. Introduction
Although the highly specialized branched cells which produce melanin
pigment granules in the integument of vertebrates have been known and
described for nearly a century, it is only within recent years and chiefly
through the use of experimental methods that their true nature has been
revealed and their origin definitely linked with a transitory embryonic struc-
ture, the neural crest. Certainly, for all practical purposes the old and
often heated controversy over the origin of the vertebrate pigment cell may
be considered, at long last, to have come to an end. The purpose of this
paper is to review the experimental evidence upon which the neural crest
origin of the mammalian pigment cell is based and to show that this special-
ized cell is essential for the pigmentation of hair.
II. Source of Pigment Cells in the Embryo
The techniques of modern experimental embryology have made possible
the use of special methods for ascertaining causal relationships in develop-
mental processes. The establishment of the origin of the vertebrate pigment
cell from the neural crest may be cited as one of the striking examples of
the application of the experimental method of attack. The mammalian
embryo, owing to its development in utero, is by no means as well suited for
experimentation as that of either the amphibian or the bird. It has there-
fore been used very little in experimental embryological research. About
ten years ago it was found that embryonic mouse tissues would grow and
differentiate quite normally in the coelomic cavity of chick embryos (Rawles,
1940). This finding led to a systematic attack of the problem of pigment
cell origin in a mammal for the first time. The experimental procedure has
*I am indebted to my husband, Mr. John S. Spurbeck, for his skilful preparation
of the illustrative material.
1
2 MARY E. RAWLES
paralleled closely that used with success by Eastlick (1939) and Ris (1941)
for determining the origin of pigment cells in birds (fowl) namely, the
transplantation of isolated portions from various axial levels of potentially
pigmented embryos at successive stages in their development, to the coelom
of White Leghorn chick host embryos of approximately 2*4 days incubation.
Isolates introduced into the embryonic coelom become attached readily either
to the coelomic wall (Fig. 2) or to the mesenteries (Fig. 4) and are well
vascularized by the blood vessels of the chick host. The surface of the graft
is enveloped by the smooth transparent host peritoneum. Because the im-
planted tissue tends to round up into a ball or vesicle, hairs when present
are, as a rule, found directed towards the interior of the graft rather than
growing directly into the body cavity (Figs. 2 and 3). The intracoelomic
grafting method has a decided advantage for pigmentation studies, for in
the coelom the grafted tissues may continue their development for a long
period of time (approximately 17 days or even longer if necessary) which
allows ample time for the differentiation of melanin granules within the
pigment cells and for the development of hair. Before entering into a dis-
cussion of the experimental data upon which the neural crest origin of the
mammalian pigment cell is based, it may be of advantage to consider briefly
the morphological development of the neural crest.
The neural crest of the mouse follows closely the developmental pattern
described not only for many other mammalian embryos (cat, rabbit, roe,
ground squirrel, rat, man) but also birds (chick, starling), see Holmdahl
(1928). It arises very early in development, disperses its cells, and dis-
appears as a definite morphological structure, all within a short period of
time (approximately three days). In the mouse the crest appears first in
the midbrain region shortly after the formation of the fourth pair of somites
and gradually progresses caudally as more and more somites are added.
After the closure of the neural tube, it may be seen as an accumulation
of rather loosely arranged cells interposed between the neural tube and the
overlying ectoderm. From this mass, cells begin to wander out on each
side in two directions; laterally toward the somite, pushing between it and
the overlying ectoderm and ventrally, along the sides of the neural tube,
between it and the somite. In transverse sections these two strands of cells
often show a forked configuration. The crest cells soon become intermingled
with mesenchyme cells of the developing somite and cannot be distinguished
from them. Herein lies the main difficulty that has been encountered in
tracing the prospective fate of neural crest cells. Owing to the characteristic
progressive, wavelike development of the crest in an anteroposterior direc-
tion and the fact that at any given level it completes its development rapidly
and ceases to exist as a definite rudiment, it is not found in any vertebrate
as a continuous body extending throughout the length of the embryo.
ORIGIN OF THE MAMMALIAN PIGMENT CELL 3
By the time a mouse embryo has developed approximately twenty pairs
of somites, all stages in the development of the crest may be found in the
trunk region of one embryo by examining transverse sections at different
axial levels. In the youngest, posterior-most region where segmentation of
the paraxial mesoderm into somites is going on, the crest will be found as
a rather discrete body overlying the dorsal portion of the neural tube; more
anteriorly it will be found in its migrating phase with cells streaming out
laterally and ventrally (Fig. 1); and still more anteriorly the crest will
have completed its migration from the neural tube. The dorsal boundaries
of the neural tube are now sharply defined and the crest is no longer found
as a definite morphological structure. The region between the neural tube
and the somites has become filled with mesenchyme contributed by both
the crest and the somite but the two components are histologically in-
distinguishable.
It is readily seen, then, that a segment of neural tube isolated from a
level at which the neural crest has not yet begun to migrate would contain
the entire prospective crest material, while a segment of neural tube isolated
from a level at which the crest had completed its migration would contain
no crest cells whatsoever. Similarly, portions of the adjacent somite and
lateral plate isolated before the crest cells had begun to migrate from the
neural tube would be crest-free, while the same type of isolation after the
crest cells had entered the region would contain numerous cells of crest
origin. By allowing appropriately made isolates to continue their growth
and differentiation in a site known to be favorable to pigment cell develop-
ment, such as the embryonic chick coelom, it thus becomes possible to deter-
mine whether or not there is any relationship between the appearance of
pigment cells in the graft and the phase of development of the neural crest
at the time the isolation was made.
To obtain proof that pigment cells take their origin from the neural crest,
it is necessary to correlate their presence or absence in the grafts with the
morphological development of the neural crest at the various ages and axial
levels tested and to show that only those tissues containing neural crest or
its migratory cells can produce pigment. In the experiments now under
discussion, these conditions have been met (Rawles, 1947). Data obtained
from an extensive series of grafts (over 200) from embryos of a homozygous
black strain of mouse (C57), ranging in age from 4 to 40 pairs of somites,
have demonstrated clearly that only those tissues containing neural crest
(prospective crest, histologically recognizable crest, or cells which have mi-
grated from the crest) can produce pigment cells in grafts. Skin and hairs
structurally normal but entirely pigment-free (white) developed regularly
in grafts from which the neural crest was excluded (compare Figs. 7 and 8).