On the backroads to cellular asymmetry

Asymmetric cell division is a process whereby one cell generates two daughter cells that differ in size or developmental potential. Asymmetric cell divisions were first described during the initial, cleavage-like divisions of the zygote, where they contribute to the establishment of the body axes in some organisms. More recently, however, the identification of cell-fate determinants that are segregated asymmetrically in dividing somatic cells has focused the interest of the field on later stages of development. The importance of asymmetric cell divisions for stem cell biology has, in particular, generated a strong interest in the molecular mechanisms that guide this important biological process.FIG1 

Much of what we know about asymmetric cell division comes from two model organisms: the worm Caenorhabditis elegans and the fruitfly Drosophila melanogaster. Their study has taught us much of what we know about segregating determinants and the molecules that guide their asymmetric localization during mitosis. The Springer Press book Asymmetric Cell Division (in the Progress in Molecular and Subcellular Biology series), edited by Alvaro Macieira-Coelho, wants to go beyond these`classical' model systems. In a series of reviews, it also includes those model organisms that are less well studied and that are not covered in the standard review literature. It is obvious that this strategy cannot generate a textbook that would be useful for teachers who want to cover asymmetric cell division in their lectures. Nor is the book suitable for students who are confronted with the field for the first time. The book is targeted at scientists working in the field who want to collect information from other model systems, or who are looking for a collection of in-depth reviews that cover some of the latest developments in the field.

The book can be conceptually subdivided into four parts: in the first, a set of reviews describes asymmetric cell division in plants, whereas the second section covers model systems that are less well studied but that are interesting from an evolutionary point of view. This is followed by a third section that covers asymmetric cell divisions in Drosophila and in mammalian stem cells in the nervous system and in the ovary, as well as in the human placenta and ovarian surface epithelium. The book concludes with a final part that describes cancer stem cells and the asymmetric segregation of DNA strands, two emerging topics in asymmetric cell division research.

Plants have a particular need for asymmetric cell divisions, as cell migration or even long-range morphogenetic fields are not available as mechanisms for developmental patterning. The first review by Renze Heidstra focuses on asymmetric cell division in the model plant Arabidopsis thaliana. Following an introductory chapter on general features of plant cell division, it covers what we know about asymmetric cell division during the early zygote stages, as well as the postembryonic stem cell divisions that are characteristic of plant meristems. The review finishes with chapters on lateral root development, stomata formation and pollen development, which largely describe the mutants that affect these tissues and the respective gene functions. A second review, by R. M. Ranganath, covers asymmetric cell division in flowering plants. As in the first review, Arabidopsis is the main topic, and it is a little unfortunate that the significant redundancy that exists between these two chapters was not avoided by better editorial coordination. As in the first review, both embryogenesis and adult meristem stem cells are covered, but a stronger emphasis is given to gametogenesis and the various asymmetric divisions that occur during male and female gamete formation.

The next two chapters by Thomas Bosch and David Weisblath deal with Hydra and the leech Helobdella robusta, and cover two of the most exotic models of asymmetric cell division research. Both articles start with a detailed introduction into the evolution of these model organisms and their developmental peculiarities. Needless to say, these reviews have to be descriptive because the work undertaken in these organisms mostly asks whether principles developed in other species can be applied to these organisms as well. Unusually for a review, both chapters contain a large proportion of work by the authors themselves - some even unpublished. However, the authors do a good job in describing how general principles can be derived from following cell biological processes through evolution and, for me, these were certainly two of the more-insightful chapters in the book.

The third part of the book covers more-mainstream model organisms and deals with Drosophila and mouse models of germline and neural stem cells,as well as asymmetric cell division in the immune system. In the first review of this section, Pierre Fichelson and Jean-René Huynh describe asymmetric cell division in the Drosophila ovarian germline. Drosophila germline development is one of the best-understood model systems for stem cell biology and has been extensively covered in many excellent reviews of recent years. Although this review cannot avoid sharing some redundancy with these other papers, the chapter stands out because it specifically covers aspects of intrinsic asymmetry in ovarian stem cells that are usually less emphasized. It finishes with an interesting chapter on asymmetric division during meiosis that integrates work from both vertebrate and invertebrate models.

A second review by Takaki Miyata in this section covers the role of asymmetric cell division during mammalian brain development. This is a controversial topic, and multiple models exist for how progenitor divisions might create both self-renewing and differentiating daughter cells. The review opens by discussing the role of Numb, a segregating determinant that has been identified in Drosophila, but whose function in mice remains controversial. It is unfortunate that very recent data that shed important light on this conflict are not included, most likely owing to the lengthy publication process of a book. The remainder of the review draws interesting comparisons between the developing mammalian brain and the Drosophilacentral nervous system. Unlike many other reviews, it emphasizes the differences between the two systems and places particular emphasis on cell culture models and fate regulation by the Notch/Delta system. The review defines a model in which cells enter a `moratorium' period shortly after division, during which intrinsic differences between daughter cells can still be overridden by external signals.

Ivana Gaziova and Krishna Moorthi Bhat contribute a review on Drosophila embryonic neuroblasts that describes in great detail the terminal and self-renewing asymmetric cell divisions in the Drosophila embryonic nervous system. Unlike many of the reviews that exist on this topic, the text does not focus on the machinery for asymmetric cell division, but includes some less well-covered data on particular defined lineage decisions. Among these are results from the authors themselves, as well as data from Gerhard Technau's laboratory suggesting a role for Cyclin E in regulating particular asymmetric divisions. The final review in this part of the book covers asymmetric cell divisions in the human placenta and in stem cells in the fetal ovarian surface epithelium. This is clearly a very specialized review that focuses to a large extent on work by the authors themselves and presents more-original data than review-type summaries. Although interesting for those working in the immediate field, it will probably be hard to grasp for the general reader.

The book finishes with two reviews that cover emerging topics in asymmetric cell division research. In the first, Emmanuel Caussinus and Frank Hirth cover asymmetric cell division in stem cells with a particular focus on cancer stem cell biology. This review focuses almost entirely on results from Drosophila, with only a short discussion of cancer stem cells in vertebrates. Since this has been a very active field recently, this focus leaves a sufficient amount of new data unreported. The long delay that occurs between the submission and publication of a book is an inherent problem of this format and one that compromises timeliness; this becomes a particular problem when a book is reviewing a field that is moving rapidly. Recent data on the role of mitotic kinases in tumour suppression, for example, are not included. Nevertheless, the review gives a nice introduction into an emerging field and provides a balanced view.

The final review is by the editor himself. Alvaro Macieira-Coelho covers the asymmetric segregation of DNA in fibroblasts. This topic is certainly somewhat removed from the mainstream, and it is a little unfortunate that the more-recent experiments on asymmetric DNA strand segregation (or the lack thereof) in mammalian stem cells are not included. Again, the review focuses largely on data from the author's laboratory and certainly expresses views that are slightly provocative.

Altogether, this is a loose collection of reviews that could have just as well appeared as individual articles in one of the major review journals. It is quite likely, however, that some of the articles would not have survived the stringent review process that is applied by some of these journals. This is not a book I would have on my bedside (and I would certainly not recommend it to anyone who is not particularly interested in asymmetric cell division). It is probably also not a book that I would buy for my own use. However, it would be appropriate for a biology department's library. Many of us -particularly in the stem cell field - are interested in the mechanisms of asymmetric cell division, and the book is a welcome addition to the more-mainstream articles published by review journals. I personally would find a collection of individual PDFs more useful; such a format could avoid some of the problems of timeliness that are inherent when covering such an active and fast-evolving field. In my view, the field of asymmetric cell division is still too dynamic to be covered by a textbook and, once it is, such a textbook would have to be more basic, more coherent and less opinionated. Scientists or students, however, who work in this field and who have already read some of the mainstream review articles, might find this book a useful addition for understanding the less well-covered areas of asymmetric cell division research.