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Richard D. Campbell

Bio: Richard D. Campbell is an academic researcher from University of California, Irvine. The author has contributed to research in topics: Lernaean Hydra & Interstitial cell. The author has an hindex of 19, co-authored 46 publications receiving 1948 citations.

Papers
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Journal ArticleDOI
TL;DR: The results indicate that more than 90% of hydra epithelial cells are actively proliferating with a cell cycle duration about equal to the tissue doubling time, and that the population of epithelium is self-sustaining requiring no input by differentiation from other cell types.
Abstract: The cell cycle parameters of epithelial cells of Hydra attenuata are described. Specifically the rate of proliferation and the fraction of proliferating cells have been determined under conditions of defined growth rate. Techniques involved standard methods of cell cycle analysis using histological and tissue maceration preparations; pulse-chase and continuous labelling with [ 3 H]thymidine followed by autoradiographic analysis, and microspectrophotometric determination of nuclear DNA content in single cells. The results indicate that more than 90% of hydra epithelial cells are actively proliferating with a cell cycle duration about equal to the tissue doubling time. In well fed hydra the average cell cycle is about 3 days long. S period is 12-15 h, G 1 0-1 h, and mitosis 1.5 h. Most of the cell cycle consists of a long G 2 period of variable duration (24-72 h). The results provide no evidence for a subpopulation of rapidly proliferating cells as predicted by ‘growth zone’ models of hydra morphogenesis. The results also indicate that the population of epithelial cells is self-sustaining requiring no input by differentiation from other cell types. The long and variable G 2 period means that DNA synthesis and the following cell division are effectively uncoupled such that inhibitors of DNA synthesis may not stop epithelial cell division. The variable nature of the G 2 period suggests it as a possible point of control of hydra growth.

276 citations

Journal ArticleDOI
TL;DR: The cell cycle parameters of interstitial cells in Hydra attenuata have been determined by using maceration preparations and histological sections, and the lengths of G 1, S, G 2 and M were determined by standard methods of cell cycle analysis using pulse-chase and continuous labelling with [ 3 H]- and [ 14 C]thymidine as mentioned in this paper.
Abstract: The cell cycle parameters of interstitial cells in Hydra attenuata have been determined. Interstitial cells were classified according to cluster size in which they occur (1, 2, 4, 8 or 16 cells) and morphology using maceration preparations and histological sections. The lengths of G 1 , S , G 2 and M were determined by standard methods of cell cycle analysis using pulse-chase and continuous labelling with [ 3 H]- and [ 14 C]thymidine. Nuclear DNA contents were measured microfluorimetrically. All classes of interstitial cells proliferate but the cell cycle of large interstitial cells occurring singly or in pairs is longer than that of interstitial cells occurring in clusters of 4, 8 and 16 cells. The S -phase is 11-12 h long and G 1 is less than 1 h for all classes of interstitial cells. G 2 is 3-4 h long for interstitial cells in clusters of 4, 8 and 16 cells giving these cells a total cell cycle duration of 16-17 h. In contrast, large interstitial cells occurring as singles and in clusters of 2 have G 2 durations ranging from 4 to 22 h. Two subpopulations can be discerned among these cells, one having a G 1 of about 6 h and a total cell cycle of about 19 h, the other having an average G 2 of 14 h and a total cell cycle of about 27 h. The differences in cell cycle duration appear to be associated with interstitial cell function. Cells having a short cell cycle are probably committed to nematocyte differentiation, while large interstitial cells having long and variable cell cycles appear to be undetermined stem cells responsible for proliferating further interstitial cells. The variable length of G 2 in these cells suggest it as a possible control point.

223 citations

Journal Article
TL;DR: Cells having a short cell cycle are probably committed to nematocyte differentiation, while large interstitial cells having long and variable cell cycles appear to be undetermined stem cells responsible for proliferating furtherinterstitial cells.
Abstract: The differentiation of nerve cells and nematocytes in Hydra attenuata has been investigated by labelling interstitial cell precursors with PHJthymidine and following by autoradiography the appearance of labelled, newly differentiated cells. Nematocyte differentiation occurs only in the gastric region where labelled nematoblasts appear 12 h and labelled nematocytes 72—96 h after addition of 2H thymidine. Labelled nerves appear in hypostome, gastric region, and basal disk about 18 h after addition of 3H thymidine. The lag in the appearance of labelled cells includes cell division of the precursor as well as differentiation since nerves and nematocytes have 2JI postmitotic nuclear DNA content. A cell flow model is proposed for interstitial cells and their differentiated products. Stem cells occur as single interstitial cells or in pairs. Per cell generation about 60 % of the daughter cells of stem cell divisions remain stem cells and about 40 % differentiate nerves and nematocytes. Nerves differentiate directly from stem cells in about 1 day. Nematocyte differentiation requires 5-7 days including proliferation of a cluster of 4, 8, 16 or 32 interstitial cells and differentiation of a nematocyst capsule in each cell. The numbers of interstitial cells and nematoblasts predicted by the cell flow model from the rates of nerve differentiation (900 nerves/day/ hydra), nematocyte differentiation (1760 nematocyte nests/day/hydia) and stem cell proliferation (stem cell cycle = 24 h), agree with the numbers of these cells observed in hydra. The number of stem cells per hydra is 3000-6000 depending on assumptions about the time of determination. The ratio of nematocyte to nerve differentiation averaged over the whole hydra is 3:1. In the hypostome and basal disk interstitial cell differentiation occurs exclusively to nerve cells while in the gastric region the ratio of nematocyte to nerve differentiation is about 7:1.

190 citations

Journal ArticleDOI
TL;DR: It is concluded that hydra consisting only of epithelial cells are capable of essentially normal development and only in some quantitative aspects do I cell-free hydra develop abnormally.
Abstract: Hydra attenuata were rendered free of interstitial cells (I cells) and interstitial cell derivatives by colchicine treatment. These hydra were then cloned and cultivated for 18 months and their developmental capacities were studied. Some experimental hydra possessed a few (about 1% of the normal numbers) interstitial cells and retained this low level during prolonged culture and active growth without the differentiation of I-cells into specialized cells. Other hydra were completely freed of interstitial cells by the colchicine treatment. Maceration and histological analyses showed that once a hydra is freed of all interstitial cells it does not recover them, nor do its buds contain interstitial cells. I cell-free hydra also lack nerve cells, nematocytes, gametes and endodermal gland cells, and the tissue consists only of ectodermal and endodermal epithelial cells. Hydra completely lacking interstitial cells grow, bud, exhibit tissue renewal patterns, regenerate and preserve polarity generally typical of normal hydra. I cell-free hypostomal tissue has inductive capacity, as does normal hypostomal tissue, when implanted in I cell-free or normal gastric tissue. Regenerating I cell-free tissue undergoes precocious determination as does normal tissue. Only in some quantitative aspects do I cell-free hydra develop abnormally. We conclude that hydra consisting only of epithelial cells are capable of essentially normal development.

176 citations

Journal ArticleDOI
TL;DR: Tissue recruitment from the parent ends at the time that tentacle rudiments appear on the bud, and thus, tissue recruitment and hydranth morphogenesis are separate processes.
Abstract: Ten bud stages are defined and their profiles illustrated. A fate map of the developing bud of Hydra attenuata was made using vital intracellular marking. Marks made at increasing distances from the young bud tip end up in increasingly more proximal regions of the bud. There is no major difference between the recruitment patterns of cells from above, below and lateral to the bud tip. The angular positions of cells on the parent is directly correlated with their final angular positions on the bud axis. Therefore, tissue is recruited in concentric rings around the young bud tip and is distorted directly outward into the bud column. At the youngest bud stages, the fate map of the bud extends about 180° around the parent. Tissue recruitment from the parent ends at the time that tentacle rudiments appear on the bud. Thus, tissue recruitment and hydranth morphogenesis are separate processes.

140 citations


Cited by
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Book ChapterDOI
TL;DR: This chapter reviews the morphological information on intercellular junctions derived from thin-sectioning, negative staining and freeze-cleave techniques, as well as from x-ray diffraction and biochemical investigations, and correlates the structural parameters with known or proposed physiological functions.
Abstract: Publisher Summary Intercellular junctions are specialized regions of contact between the apposed plasma membranes of adjacent cells, and recent evidence suggests that they are essential for the development of multicellular organisms. They provide the structural means for groups of cells to interact in certain defined ways, and thereby enable them to create structures of higher order. This chapter reviews the morphological information on intercellular junctions derived from thin-sectioning, negative staining and freeze-cleave techniques, as well as from x-ray diffraction and biochemical investigations, and correlates the structural parameters with known or proposed physiological functions. The membrane structure of intercellular junctions is described. Membrane proteins can be divided into two groups: peripheral and integral. Peripheral membrane proteins are believed to be associated with the membrane surface, based on the observation that they are held to the membrane by rather weak noncovalent interactions, and are not strongly associated with membrane lipids. Only mild treatments, such as an increase in ionic strength of the medium or the addition of a chelating agent, are needed to dissociate them molecularly intact from the membrane. Furthermore, in the dissociated state they are relatively soluble in neutral aqueous buffers. In contrast, integral membrane proteins appear much more strongly bound to the lipid matrix, since they can be dissociated from the latter only by drastic treatments with chemicals such as detergents, protein denaturants, and organic solvents. The diversity in structure and function of intercellular junctions offers an exciting field for future research in which morphologists, physiologists, and biochemists should be able to make significant contributions to the knowledge of how individual cells interact to form structures of higher order.

1,292 citations

Journal ArticleDOI
23 Mar 1995-Nature
TL;DR: A linear zipper of molecules that mirrors the linear structure of the intracellular filaments with which cadherins associate may provide a mechanism to marshal individual molecular adhesive interactions into strong bonds between cells.
Abstract: Crystal structures of the amino-terminal domain of N-cadherin provide a picture at the atomic level of a specific adhesive contact between cells. A repeated set of dimer interfaces is common to the structure in three lattices. These interactions combine to form a linear zipper of molecules that mirrors the linear structure of the intracellular filaments with which cadherins associate. This cell-adhesion zipper may provide a mechanism to marshal individual molecular adhesive interactions into strong bonds between cells.

1,207 citations

Journal ArticleDOI
TL;DR: Simulation of the differential adhesion driven rearrangement of biological cells shows that self-organization due to few basic cell properties alone are enough to explain a number of biological phenomena.
Abstract: We show that differential adhesion with fluctuations is sufficient to explain a wide variety of cell re- arrangement, by using the extended large-Q Potts model with differential adhesivity to simulate different biological phenomena. Different values of relative surface energies correspond to different biological cases, including complete and partial cell sorting, checkerboard, position reversal, and dispersal. We examine the convergence and temperature dependence of the simulation and distinguish spontaneous, neutral, and activated processes by performing simulations at different temperatures. We discuss the biological and physical implications of our quantitative results.

800 citations

Book ChapterDOI
TL;DR: This chapter summarizes the findings and hypotheses of cancer metastasis and elucidates the complex mechanisms involved in the pathogenesis of metastasis.
Abstract: Publisher Summary This chapter summarizes the findings and hypotheses of cancer metastasis and elucidates the complex mechanisms involved in the pathogenesis of metastasis. The development of a metastasis is dependent on the interplay of host and tumor cell properties. The process is complex, highly selective, and represents the end stage of several destructive events from which few tumor cells survive. Malignant neoplasms may consist of a variety of subpopulations of cells with differing capabilities for invasion and metastasis. Only a few tumor cells within a primary neoplasm may actually invade blood vessels, and of those, even fewer survive in the circulation. The unique characteristics of tumor cells, including modifications in cell surface properties, adhesive capacities, cell motility, and enzyme secretion, are of paramount importance in determining the eventual outcome of the metastasis. Such acquired properties of malignant cells allow for interaction with host tissues and cells, which leads to tumor cell survival and growth. Three mechanisms are invoked to explain tumor cell invasion—(1) the rapid multiplication of malignant cells leading to growth and infiltration by mechanical pressure, (2) the destruction of host tissue by the products of the tumor cell, and (3) the lack of tumor cell adhesiveness accompanied by an increase in the cell motility.

738 citations

Journal Article
TL;DR: The educated lavman, for whom this book is intended, will find the author's leaps from the level of the quoted material into sophisticated physical chemistry and back again disconcerting at least, if not completely confusing.
Abstract: Clearly, the possibility that Van Peenen's statements are correct exists, but no molecular geneticist would contend that these assertions have been established, in any but a very few cases, which appear at present to be atypical. The educated lavman, for whom this book is intended, will find the author's leaps from the level of the quoted material into sophisticated physical chemistry and back again disconcerting at least, if not completely confusing. It can be said, however, that the authors have assembled an excellent group of illustrations; lecturers in elementary genetics wishing to locate clear illustrations to use as slides would do well to look in this book first.

652 citations