Pattern formation and developmental mechanisms

Pattern formation

and developmental Editorial

overview

Peter Gruss and William Max Planck Institute,

Gattingen,

mechanisms

Germany

McGinnis

and Yale University,

New Haven,

USA

Current Opinion in Genetics and Development 1993, 3:553-555 In 1828, Karl Ernst von Baer derived four generalizations from his vertebrate embryological studies that are known today as von Baer’s laws. These laws stipulate that the general features appear earlier in the vertebrate embryo than do the specialized features, that a less general character develops from a more general character, that each embryo of a given species, instead of passing through the adult stages of other animals, departs more and more from them, and finally, that the early embryo of a higher animal is never like a lower animal, but only like its early embryo. Darwin incorporated these thoughts in his Origitz oj’Species, thereby giving them an evolutionary interpretation. Consequently, key events during its de\ielopment of many vertebrate species must share a common basis. As a result of the marriage of genetics with molecular biology and experimental embryology, we now know that the molecular mechanisms of some basic developmental control processes are related among widely diverged classes of animals, both invertebrate and vertebrate. These known and emerging similarities in developmental control mechanisms can often only be detected at the molecular level, and link the embryology of animals that von Baer may have believed were related, but could not have hoped to link at the level of embryonic morpholo,gy. In this issue of Cur-t-ml Opittiott in Genetics am/ Delvloptttettl, the reviews l-q, leading scientists present a comprehensive overview covering the molecular basis of development in invertebrate and vertebrate species. The papers highlight molecular control events of development and show that there is an evolutionary conservation of basic control mechanisms. To paraphrase Jacques Monad. what is true for the fruittly in developmental mechanism, is conceptually also true for the elephant. Two of the earliest decisions to be made by an animal embryo are which end is forward and which side is up. In Drosopl~ih, the determination of clorsa-iventral (&VI polarity in the early embryo is dependent on an intricate series of molecular conversations between the developing embryo and surrounding somatic follicle cells that eventually result in the nuclear localization of the dorsal protein in ventral embqlonic nuclei. Steward and Govind (pp 556561) review recent progress in

this field, including the similarities between the early ISV patterning system and the mammalian IxB/NFxB control pathway.

Drosophikz, the early embryonic controls for anteriorposterior (A-P) patterning are intimately linked to the placement of germ-cell determinants in the most posterior regions of the Drosophila egg. Wilson and Macdonald (pp 562-565) describe how the Drosophila posteriorgroup genes regulate the assembly and placement of the ‘pole plasm’ that assigns germ-cell fate. After the general A-P and D-V coordinates of the Drosophila embryo are assigned, subregions of the A-P and D-V axis are sequentially specialized by the action of localized gap transcription factors that cross-regulate each other’s expression boundaries, as well as refine the patterns of downstream genes that control the metameric pattern of the embryo. Hoch and J3ckle (pp 566-573) review recent progress in the understanding of the mechanisms that generate stripes of gene expression in a multinucleate syncytial embryo. These are among the best understood developmental controls at the detailed mechanistic level. III

After the process of cellularization in Drosophila, the patterning genes that control the metameric pattern of the embryo increasingly rely on processes of cell-cell communication to achieve and maintain ;I normal body plan. Two crucial proteins that interact in this process are engrailed. a homeodomain transcription factor, and wingless, a secreted growth factor, which appear to be crucial parts of an evolutionarily conserved .system for controlling the spatial patterq of a growing field of cells. In the epidermis of Dt-osophik~, this system is used to assign and maintain compartmental boundaries within segments, and Kornberg and Tabata (pp 585-593) review how the system is initially activated, and how other segment polarity genes of Drosophila are believed to participate in the patterning of growing segments. Another fascinating system that is also linked to the process of segmentation in Drosophih as well as apparently segmentation in vertebrates is the family of Pax genes. These genes, which encode transcription factors containing paired domains and occasionally homeodomains, are used at multiple steps in the Drosophila patterning hierarchy, and No11 (pp 594-605) reviews the roles of paired, gooseberry and other Pgx-family gene functions in the

Abbreviations A-P-anterior-posterior;

AS-C-achaere-scufe

@ Current

complex;

Biology

D-V-dorsal-ventral;

Ltd ISSN 0959-437X

HOM-homeotic.

553

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Pattern

formation

and develoDmenta1

mechanisms

process bf segmentation and beyond. No11 also reviews the evolutionary history of the Pu.x genes, which are highly conserved in mammals. Mutations in Pm genes have been shown to underlie mouse and human developmental patterning defects, making this one of the best understood families at the genetic level in vertebrates. One of the classic families of patterning genes in Drosophila are the homeotic (HOM) genes, which encode homeodomain transcription factors. Although there are relatively few genes (eight in total), they exert a significant influence ori segmental/regional identities, and the evidence for their structural and functional conservation in mammals and other animals in controlling regional identities in cellular fields has grown dramatically over the past few years (see the reviews by Krumlauf, pp 621-625; and Morgan and Tabin, pp 668-674). Morata (pp 606-614) reviews recent progress on the interactions between the Drosophila homeotic genes and the evidence that many compete for similar downstream target genes. In fact, it appears that mammalian homologs of some Drosophila HOM genes can compete for the same targets in Drosophila embryos. Many homeotic target genes have been identified in the past year and surely many more remain to be discovered. The nematode Caenorbabditis elegans also contains a cluster of HOMlike genes. Biirglin and Ruvkun (pp 615-620) review recent exciting results that indicate this cluster of highly conserved genes also has a role in assigning regional identities along the A-P axis of the nematode body plan. Structural studies of the C elegans HOM complex indicate that it retains novel homeobox genes such as ceb23, which should be very instructive about the functional evolution of the homeotic genes. There is currently a murky area in the Drosophila developmental genetic hierarchy between the regional patteming genes such as the homeotics, and genes that assign fates to individual cells. One bright spot in this area is represented in the review by Jimenez and Modolell (pp 626-632). They describe new progress in understanding how the acbuetescute complex (AS-C) genes and their associated co-factors regulate each other to assign neural cell identities. The AS-C genes encode basic-region helixloop-helix transcription factors, which are also highly conserved in mammals, where they may also be involved in determining tissue- and cell-type during development. Many of the foregoing reviews focus on the genetic roles of transcriptional regulators in developmental patterning. Surely as important, though currently not as well understood in most genetic pathways, are the developmental decisions that result from post-transcriptional regulatory mechanisms. Rio (pp 574-584) reviews the mechanisms of splicing regulation and the importance of regulated splice-site selection in the sexual determination of Drosophila somatic cells. The existence of multiple isoforms for important transcription factors involved in patterning (including many of the proteins described in the other reviews) suggests that much functional regulation occurs through exon inclusion and exclusion. The general body plan of all vertebrate embryos becomes visible shortly after gastrulation because during

this process the rostro-caudal, D-V and left-right axes become evident. This led Lewis Wolpert to say that it is not birth, marriage, or death, but gastrulation that is truly the most important time in your life. Based on the expression patterns and available mutational analyses of the Brachyury, and goosecoid genes and the fork heud gene family, Beddington and Smith (pp 655-661) suggest that the development of early gastrula stages in the mouse, Xenopus, chick and fish is remarkably similar. This should encourage researchers to take advantage of the strength of individual systems such as the ease of manipulating Xenopus and chick embryos, the ability to mutate genes in the mouse by site-directed mutagenesis, and the transparency and potential for genetic analysis in zebra fish, and yet arrive at general conclusions. Mullins and Niisslein-Volhard (pp 648-654) describe the establishment of genetic methods in the zebra fish, Bracbyctanio rerio, which, due to rapid development, the large size of the embryo and its development outside the mother’s body, is ideal for genetic analysis, although it will still take some time to optimize methods required for the cloning of the mutated genes. Xenopus has proven to be an excellent system for the study of induction events. Several recent reviews on mesoderm induction summarize the findings. Two developmental processes are concerned with cell interactions that take place in the mesoderm during gastrulation: the first is dorsalization, which can convert ventral mesoderm cells to a more dorsal fate; the other is the community effect discussed by Gurdon ef al. (pp 662667). The community effect involves an interaction among muscle progenitor cells of an amphibian gastrula, which is necessary for the initiation of muscle-specific gene expression. Interestingly, these findings may have a wider developmental significance. The community effect might operate in many different developmental situations where a gradient needs to be transformed into two or more uniform populations of cells sharply demarcated from each other. The induction and patterning of the neural plate is also controlled by a series of induction events - previously suggested by Spemann - that occur initially between mesodemial and ectodermal cells and later between cells of the neural plate itself. With the help of molecular markers, the hierarchy of control events involved can be dissected as detailed by Ruiz i Altaba and Jesse11 (pp 633-640). Following neurulation, neural crest cells migrate from the dorsal apex of the neural tube and contribute to a variety of structures. Along the rosto-caudal axis, HOX genes are key regulators of axial patterning and may also specie positional identity along the neural tube. As these genes are also expressed in the neural crest in a corresponding manner, they might confer regional differences in crest migration patterns and cell fate (Bronner-Fraser, pp 641-647). Based initially on dominant gain and, more recently on loss of function mutations there is no doubt that the Hon;/HOM complexes play a vital role in the axial patterning of multiple tissues. Details of the role of Hox genes in the patterning of the rosto-caudal axis can be

Editorial

overview

Cruss and McGinnis

found in the reviews by Krumlauf, and Morgan and Tabin, which detail the patterning of the limb axes. However, the events controlling the precise activation and deactivation of Hox/HOMgene activities in time and space remain to be elucidated.

to studying the development of higher organisms, for it will be the synergism of individual contributions that will ultimately present us with a view of the whole.

The link between ontogeny and phylogeny was recognized by anatomists more than a centuty ago. Thus, we should not be surprised that evolutionary kinships are evident also at the molecular level. This issue convincingly demonstrates the advantages of a multi-system approach

P Gruss, Max Planck Institute of Biophysical Chemistry, Karl Friedrich Bonhoeffer Institute, Department of Cell Biology, PO Box 2841, Am Fa%berg, 3400 Gettingen, Germany. W McGinnis, Department Yale University, PO Box necticut 06511, USA

of Molecular Biophysics 6666, 260 Whitney Avenue,

and Biochemistry, New Haven, Con-

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