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Publisher: Wiley-Blackwell , Year: Description: Necessary Developmental Biology is a detailed, richly illustrated introduction to the developmental biology in all aspects. The third edition of this famous textbook has been expanded and revised in a clear and accessible style In addition, an accompanying website provides instructional materials for use by both students and lecturers, including animated development processes, a photo gallery of selected model organisms and all artworks in downloadable format.

With an emphasis throughout on the facts that underpin the main conclusions, this book is an important text for both introductive and advanced developmental biology courses. Second Edition reviews: "For anyone interested in developmental biology, the second edition is a must-have. Content focused on the basic science underpinning stem cell biology Covers techniques of studying cell properties and cell lineage in vivo and in vitro Explains the basics of embryonic development and cell differentiation, as well as the essential cell biology processes of signaling, gene expression, and cell division Includes instructor resources such as further reading and figures for downloading Offers an online supplement summarizing current clinical applications of stem cells Written by a prominent leader in the field, The Science of Stem Cells is an ideal course book for advanced undergraduates or graduate students studying stem cell biology, regenerative medicine, tissue engineering, and other topics of science and biology.

Download Molecular Methods In Developmental Biology books , In Molecular Methods in Developmental Biology: Xenopus and Zebrafish, Matthew Guille assembles a hands-on collection of basic and essential molecular and embryological techniques for studying Xenopus and zebrafish.

Easily reproducible and designed to succeed, these detailed methods include cellular techniques, techniques for the quantitative and spatial analysis of mRNA and proteins, and techniques for the expression of gene products in embryos. More specialized methods enable users to analyze promoters and transcription factors during early development, and include gel shift assays, as well as in vitro and in vivo footprinting.

Wherever possible, these experimental approaches are applied to both Xenopus and zebrafish. Molecular Methods in Developmental Biology: Xenopus and Zebrafish affords newcomers rapid access to a wide variety of key techniques in developmental research, and offers experienced investigators both new techniques from experts who have fine-tuned them for best results, and a plethora of time-saving tips.

State-of-the-art and readily reproducible, these powerful methods constitute today's gold-standard laboratory manual for understanding the interactions responsible for development. Wieso war John F. Weswegen waren Paganinis Finger schneller als die aller anderen Geiger? Und warum war Einstein eigentlich so schlau? Diese und viele weitere Fragen beantwortet Sam Kean in seinem neuen Buch.

We've made important advances in our scientific understanding, but despite this the clinical applications of stem cells are still in their infancy and most real stem cell therapy carried out today is some form of bone marrow transplantation. At the same time, a scandalous spread of unproven stem cell treatments by private clinics represents a serious problem, with treatments being offered which are backed by limited scientific rationale, and which are at best ineffective, and at worse harmful.

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Slack warns against fake stem cell treatments and discusses how to distinguish real from fake treatments. These pocket-sized books are the perfect way to get ahead in a new subject quickly. Our expert authors combine facts, analysis, perspective, new ideas, and enthusiasm to make interesting and challenging topics highly readable. Download Molekularbiologie Der Zelle books , "Molekularbiologie der Zelle" ist auch international das fuhrende Lehrbuch der Zellbiologie.

Vollstandig aktualisiert fuhrt es Studierende in den Fachern Molekularbiologie, Genetik, Zellbiologie, Biochemie und Biotechnologie vom ersten Semester des Bachelor- bis ins Master-Studium und daruber hinaus. Mit erstklassiger und bewahrter Didaktik vermittelt die sechste Auflage sowohl die grundlegenden, zellbiologischen Konzepte als auch deren faszinierende Anwendungen in Medizin, Gentechnik und Biotechnologie. Download Evolutionary Developmental Biology books , Although evolutionary developmental biology is a new field, its origins lie in the last century; the search for connections between embryonic development ontogeny and evolutionary change phylogeny has been a long one.

Evolutionary developmental biology is however more than just a fusion of the fields of developmental and evolutionary biology. As in mitosis, meiosis is also preceded by an S phase in which each chromosome becomes replicated to form two identical sister chromatids, so the process starts with the nucleus possessing a total DNA content of four times the haploid complement. In mitosis the sister chromatids will separate into two identical diploid daughter cells.

But meiosis involves two successive cell divisions. In the first the homologous chromosomes, which are the equivalent chromosome derived from mother and father, pair with each other. At this stage the chromosomes are referred to as bivalents, and each consists of four chromatids, two maternal-derived and two paternal-derived. Hence, alleles present at two different loci on the same chromosome of one parent may become separated into different gametes and be found in different offspring.

The frequency with which alleles on the same chromosome are separated by recombination is roughly related to the physical separation of the loci, and this is why the measurement of recombination frequencies is the basis of genetic mapping. Recombination can also occur between sister chromatids but here all the loci should all be identical since they have just been formed by DNA replication. In the first meiotic division the four-stranded bivalent chromosomes will separate into pairs which are segregated to the two daughter cells.

There is no further DNA replication and in the second meiotic division the two chromatids become separated into individual gametes. It is a primary oocyte until completion of the first meiotic division and a secondary oocyte until completion of the second meiotic division. After this it is known as an unfertilized egg or ovum. Because in the model organisms considered here fertilization occurs before completion of the second division, it is technically an oocyte rather than an egg that is being fertilized.

Eggs are larger than sperm and the process of oogenesis involves the accumulation of materials in the oocyte. Usually the primary oocyte is a rather long-lived cell that undergoes a It should be noted that the terms haploid 1n and diploid 2n are normally used to refer to the number of homologous chromosome sets in the nucleus rather than the actual amount of DNA.

Oogenesis The process of formation of eggs is called oogenesis Fig. Following sex determination to female, the germ cells become oogonia, which continue mitotic division for a period.

The germ cells are initially formed from a cytoplasmic determinant and during development they migrate to enter the gonad. Spermatogenesis generally results in the production of four haploid sperm per meiosis. Oogenesis generally results in the formation of one egg and two polar bodies PB1 has the same chromosome number but twice the DNA content as PB2.

Common features of development u considerable increase in size. Its growth may be assisted by the absorption of materials from the blood, such as the yolk proteins of fish or amphibians which are made in the liver. It may also be assisted by direct transfer of materials from other cells. This is seen in Drosophila where the last four mitoses of each oogonium produces an egg chamber containing one oocyte and 15 nurse cells. The nurse cells then produce materials that are exported to the oocyte.

Animals that produce a lot of eggs usually maintain a pool of oogonia throughout life capable of generating more oocytes. Mammals differ from this pattern as they are thought to produce all their primary oocytes before birth.

In humans no more oocytes are produced after the seventh month of gestation, and the primary oocytes then remain dormant until puberty. Although this is the conventional view, there is recent evidence for some postnatal oogenesis in mice. Ovulation refers to the resumption of the meiotic divisions and the release of the oocyte from the ovary. It is provoked by hormonal stimulation and involves a breakdown of the oocyte nucleus the germinal vesicle and the migration of the celldivision spindle to the periphery of the cell.

The meiotic divisions do not divide the oocyte into two halves, but in each case into a large cell and a small polar body. The first meiotic division divides the primary oocyte into a secondary oocyte and the first polar body, which is a small projection containing a replicated chromosome set. The second meiotic division divides the secondary oocyte into an egg and a second polar body, which consists of another small projection enclosing a haploid chromosome set.

The polar bodies soon degenerate and play no further role in development. Spermatogenesis If the process of sex determination yields a male then the germ cells undergo spermatogenesis Fig. Mitotic germ cells in the testis are known as spermatogonia. These are stem cells that can both produce more of themselves and produce cells whose destiny is terminal differentiation into sperm.

After the last mitotic division the male germ cell is known as a primary spermatocyte. Meiosis is equal, the first division yielding two secondary spermatocytes and the second division yielding four spermatids, which mature to become motile spermatozoa. Early development The process of fertilization differs considerably between animal groups but there are a few common features.

When the sperm fuses with the egg there is a fairly rapid change in egg structure that excludes the fusion of any further sperm. This is called a block to polyspermy. Fusion activates the inositol trisphosphate signal transduction pathway see Appendix resulting in a rapid increase in intracellular calcium.

This causes exocytosis of cortical granules whose contents form, or contribute to, a fert- 11 ilization membrane; and also trigger the metabolic activation of the egg, increasing the rate of protein synthesis and, in vertebrates, starting the second meiotic division.

The calcium may, in addition, trigger cytoplasmic rearrangements that are important for the future regional specification of the embryo, for example cortical rotation in Xenopus, or polar granule segregation in C. The sperm and egg pronuclei fuse to form a single diploid nucleus and at this stage the fertilized egg is known as a zygote.

A generalized sequence of early development is shown in Fig. A typical zygote of an animal embryo is small, spherical, and polarized along the vertical axis. The upper hemisphere, usually carrying the polar bodies, is called the animal hemisphere, and the lower hemisphere, rich in yolk, the vegetal hemisphere.

The early cell divisions are called cleavages. They differ from normal cell division in that there is no growth phase between successive divisions.

So each division partitions the mother cell into two half-size daughters. The products of cleavage are called blastomeres. Cell division without growth can proceed for a considerable time in free-living embryos without an extracellular yolk mass. Embryos that do have some form of food supply, either mammals that are nourished by the mother, or egg types with a large yolk mass such as birds and reptiles, usually only undergo a limited period of cleavage at the beginning of development.

This is the stage of maternal effects because the properties of the cleavage stage embryo depend entirely on the genotype of the mother and not on that of the embryo itself see Chapter 3. Different animal groups have different types of cleavage Fig. Where there is a lot of yolk, as in an avian egg, the cytoplasm is concentrated near the animal pole and only this region cleaves into blastomeres, with the main yolk mass remaining acellular. This type of cleavage is called meroblastic. Where cleavage is complete, dividing the whole egg into blastomeres, it is called holoblastic.

Holoblastic cleavages are often somewhat unequal, with the blastomeres in the yolk-rich vegetal hemisphere being larger macromeres , while those in the animal hemisphere are smaller micromeres. Each animal class or phylum tends to have a characteristic mode of early cleavage and these can be classified by the arrangement of the blastomeres into such categories as radial echinoderms , bilateral ascidians , rotational mammals.

An important type is the spiral cleavage shown by most annelid worms, molluscs, and flatworms. Here, the macromeres cut off successive tiers of micromeres, first in a right-handed sense when viewed from above, then another tier in a left-handed sense, and so on. Most insects and some crustaceans show a special type of cleavage called superficial cleavage. Here only the nuclei divide and there is no cytoplasmic cleavage at the early stages. Thus, the early embryo becomes a syncytium consisting 12 u Chapter 2 Polar body Yolk a Zygote b Cleavage c Blastocoel d Blastula e Gastrula Ectoderm Mesoderm Archenteron cavity Endoderm f Three germ layers Head g Larva Segments one another, being bound by cadherins, and will usually have a system of tight junctions forming a seal between the external environment and the internal environment of the blastocoel.

Following the formation of the blastula, all animal embryos show a phase of cell and tissue movements called gastrulation that converts the simple ball or sheet of cells into a three-layered structure known as the gastrula. The details of the morphogenetic movements of gastrulation can vary quite a lot even between related animal groups, but the outcome is similar.

The three tissue layers formed during gastrulation are called germ layers, but these should not be confused with germ cells. Conventionally the outer layer is known as the ectoderm, and later forms the skin and nervous system; the middle layer is the mesoderm and later forms the muscles, connective tissue, excretory organs, and gonads; and the inner layer is the endoderm, later forming the epithelial tissues of the gut.

The germ cells have usually appeared by the stage of gastrulation and are not regarded as belonging to any of the three germ layers.

After the completion of the major body morphogenetic movements most types of animal embryo have reached the general body plan stage at which each major body part is present as a region of committed cells, but is yet to differentiate internally. This stage is often called the phylotypic stage, because it is the stage at which different members of an animal group, not necessarily a whole phylum, show maximum similarity to each other see Chapter For example all vertebrates show a phylotypic stage at the tailbud stage when they have a notochord, neural tube, paired somites, branchial arches, and tailbud.

All insects show a phylotypic stage at the extended germ band when they show six head segments, three appendage-bearing thoracic segments, and a variable number of abdominal segments. Segments, spines and spots are not necessarily found in all animals but represent a typical external anatomy. The color scheme of ectoderm green, mesoderm orange, and endoderm yellow is used throughout the book.

At a certain stage the nuclei migrate to the periphery and shortly afterwards cell membranes grow in from the outer surface of the embryo and surround the nuclei to form an epithelium. During the cleavage phase a cavity usually forms in the center of the ball of cells, or sheet of cells in the case of meroblastic cleavage. This expands due to uptake of water and becomes known as the blastocoel. At this stage of development the embryo is called a blastula.

The cells often adhere tightly to In order that the correct orientation of a specimen can be specified, it is necessary to have terms for describing embryos Fig. If the egg is approximately spherical with an animal and vegetal pole then the line joining the two poles is the animal—vegetal axis. Unfertilized eggs are usually radially symmetrical around this axis, but after fertilization there is often a cytoplasmic rearrangement that breaks the initial radial symmetry and generates a bilateral symmetry.

In some organisms, such as Drosophila, this may occur earlier, in the oocyte; in others, such as mammals, it may occur later, at a multicellular stage. But even animals such as sea urchins, which are radially symmetrical as adults, or gastropods, which are asymmetrical as adults, still have bilaterally symmetrical early embryos. The change of symmetry means that the animal now has a distinct dorsal upper and ventral lower side. If the animal and vegetal poles are at the top and bottom, then the equatorial plane is the horizontal plane dividing the egg into animal and vegetal hemispheres, just like the equator of the Earth.

Any vertical plane, corresponding to circles of longitude, a Holoblastic b Meroblastic d Radial Fig. This is often, but not always, the plane of the first cleavage. The frontal plane is the meridional plane at right angles to the medial plane, and is often, but not necessarily, the plane of the second cleavage.

Following gastrulation most animals become elongated. The top—bottom axis is called dorsoventral and the left—right axes are called mediolateral. Some phyla, including annelids, arthropods, and chordates, show prominent segmentation of the anteroposterior axis. To qualify as segmented an organism should show repeated structures that are similar or identical to each other, are principal body parts, and involve contributions from all the germ layers.

Although most animals have an overriding bilateral symmetry, this is not exact and there are systematic deviations which make right and left sides slightly different.

For example in mammals the cardiac apex, stomach, and spleen are on the left and the liver, vena cava, and greater lung lobation are on the right. This asymmetrical arrangement is known as situs solitus. If the arrangement is inverted, as occurs in some mutants or experimental situations, it is called situs inversus Fig.

If the parts on the two sides are partly or wholly equivalent, it is called an isomerism. Morphogenetic processes Cell shape changes and movements are fundamental to early development as the embryo needs to convert itself from a simple ball or sheet of cells into a multilayered and elongated structure. The processes by which this is achieved are called gastrulation.

Although the details of gastrulation can differ substantially between even quite similar species, the basic cellular processes are common.

At later stages of development the same repertoire of processes is re-used repeatedly in the morphogenesis of individual tissues and organs. From a morphological point of view most embryonic cells can be regarded as epithelial or mesenchymal Fig. These terms relate to cell shape and behavior rather than to embryonic origin, as epithelia can arise from all three germ layers and mesenchyme from ectoderm and mesoderm.

An epithelium is a sheet of cells, arranged on a basement membrane, each cell joined to its neighbors by specialized junctions, and showing a distinct apical—basal polarity. Mesenchyme is a descriptive term for scattered stellate cells embedded in loose extracellular matrix. It fills up much of the embryo and later forms fibroblasts, adipose tissue, smooth muscle, and skeletal tissues. Epithelia and mesenchyme are further described in Chapter Cell movement Many morphogenetic processes depend on the movement of individual cells.

This is most apparent in the case of migrations, Apical specialization Junctional complexes a Basement membrane Epithelium Cell Matrix b Mesenchyme Fig. Common features of development u 15 Microfilament bundle contraction Lamellipodium Focal contacts Substratum a Fibroblast movement Apical microfilament bundles Fig.

But shorter-range movements are also important for processes such as differential adhesion or shape changes in cell sheets. The mechanism of cell movement is most apparent in fibroblasts moving on a substratum Fig. They extend a flat process called a lamellipodium plural lamellipodia which is rich in microfilaments.

This attaches to the substratum by focal attachments containing integrins, which are connected to the microfilament bundles by a complex of actin-associated proteins. The body of the cell is then drawn forward by a process involving active contraction in which myosin molecules migrate towards the plus end of microfilaments.

Cells in embryos are thought to move in essentially the same way. Instead of a large flat lamellipodium they may extend multiple thin filopodia to form the contacts. Nerve axons also elongate by a similar mechanism. At the tip is a flattened structure called a growth cone, which emits the filopodia. Cell shape can also change because of the activity of microfilament bundles and their associated motor proteins. An apical constriction in a group of epithelial cells will reduce the apical surface area and increase the length of the cells Fig.

This is often a preliminary to an invagination movement in which the cells leave their epithelium and enter the space below. Cell adhesion Vertebrate epithelial cells are bound together by tight junctions, adherens junctions, and desmosomes, the latter two types involving cadherins as major adhesion components see Appendix.

Mesenchymal cells may also adhere by means of cadherins but usually more loosely. The adhesion of early embryo cells is Apical constriction usually dominated by the cadherins as shown by the fact that most types of early embryo can be fully disaggregated into single cells by removal of calcium from the medium.

There is some qualitative specificity to cell adhesion. Cadherin-based adhesion is homophilic and so cells carrying E-cadherin will stick more strongly to each other than to cells bearing N-cadherin. The calcium-independent immunoglobulin superfamily-based adhesion systems such as N-CAM Neural Cell Adhesion Molecule , particularly important on developing neurons and glia, are different again, and also promote adhesion of similar cells.

This qualitative specificity of adhesion systems provides a mechanism for the assembly of different types of cell aggregate in close proximity, and also prevents individual cells wandering off into neighboring domains.

If cells with different adhesion systems are mixed they will sort out into separate zones, eventually forming a dumbbell-like configuration or even separating altogether Fig. In addition to the qualitative aspect of specificity, it is also known that cell-sorting behavior can result simply from different strengths of adhesion of the same system.

The process is based on the existence of small random movements of the cells in the aggregates, and the same final configuration will be reached from any starting configuration, for example from an intimate mixture of the two types, or from blocks of the two types pressed together. Classification of morphogenetic processes Similar repertoires of morphogenetic processes are re-used repeatedly in different developmental contexts Fig. This type of analysis was used to investigate the posterior group mutants in Drosophila and to show that nanos was the last-acting member of the pathway see Chapter If members of a set of mutants have one of two opposite phenotypes then the genes may again code for the successive steps in a pathway but it is likely that some or all the steps will be repressive events rather than activations.

Figure 3. Pigment is made in the spots of segment 2 following the operation of a pathway of three genes in which a represses b which represses c which represses pigment formation. Normally gene a is active everywhere except the spots, so only the spots become pigmented. It is possible to deduce the sequence of action of the genes by examining the phenotype of the double mutants.

In each case the phenotype of the double mutant is the same as that produced by the mutant of the later acting of the two genes. By looking at the phenotype of each double mutant combination, the genes can be arranged into a Pigmented Pigmented Fig.

Normally, a gene a is inactivated in three spots of segment 2, resulting in the formation of dark pigment. In a loss of function mutant of a or c the whole organism is pigmented.

In a loss of function mutant of b there is no pigment. The phenotypes of the double mutants show that b must act after a and before c. Among many other examples, this type of analysis was used to order the dorsal group genes in Drosophila see Chapter Repressive pathways are remarkably common and they can cause much confusion. The best way to understand them is, as in Fig.

In developmental biology the two conditions often refer two regions within the embryo where the same pathway is under different regulation, for example the dorsal and ventral sides. These methods are examples of epistasis analysis, because if one gene prevents the expression of another it is said to be epistatic to it.

Another method of ordering gene action in development depends on the use of temperature-sensitive mutations. In contrast to the pathway situations, this does not depend on any particular relationship between different gene products and can be used to order events in time which are mechanistically quite independent of each other. Temperature-sensitive mutants are those which display the phenotype at a nonpermissive usually high temperature, and do not show a phenotype at the permissive usually low temperature.

They are frequently weak loss-of-function alleles. They arise from changes in the conformation of the protein product which are sensitive to changes in temperature in the range compatible with embryonic survival.

The time of action of a gene may be deduced by subjecting groups of temperature-sensitive mutant embryos to the nonpermissive temperature at different stages of development. If the Developmental genetics organism ultimately displays the mutant phenotype, this means that the gene was inactivated at the time of its normal function, in other words that the gene was required during the period of the high temperature exposure. An example would be the time of action of the gene cyclops, which is needed for the induction of the floor plate in zebrafish.

Temperature-sensitive mutants are more use in poikilothermic organisms such as C. Genetic mosaics It is sometimes possible to make organisms that consist of mixtures of cells of different genotypes. These are called genetic mosaics and can be useful as they provide information about where in the embryo a particular gene is required.

For instance an embryo may consist of two territories, A and B, and a particular mutant shows a defect in B.

We can consider two informative types of genetic mosaic Fig. One has prospective A cells mutant and prospective B cells wild type, while the other has a u 25 prospective B cells mutant and prospective A cells wild type. If the organism with B cells mutant shows the abnormal phenotype, then we say that the mutant is autonomous; it affects just the region in which the gene is normally active. However, if the organism with A cells mutant shows the abnormal phenotype, then the mutant is nonautonomous because it is affecting a structure outside the domain of action of the gene.

Nonautonomy means that there must be an inductive signaling step that is affected by the mutation. However, it does not necessarily mean that the mutant gene itself codes for a signaling factor, as failure of the signaling event can be a downstream consequence of the mutation. Genetic mosaics have been widely used in Drosophila. A very useful type is made by pole-cell transplantation and consists of germ cells of one genotype in a host of a different genotype.

Such mosaics have enabled the understanding of factors controlling the patterning of the oocyte as a result of interactions with the somatically derived follicle cells of the egg chamber see Chapter Mosaics have also been used in C. In zebrafish, mosaics can be created by grafting as there is quite a lot of early cell mixing to disperse the labeled cells. In mammals, the term mosaic is usually reserved for a naturally occurring organism composed of two genetically dissimilar cells e.

X inactivation mosaic, see Chapter 10 and the term chimera is used for embryos made experimentally by cell injection or aggregation of blastocysts. Genetic mosaics should not be confused with embryos said to show mosaic behavior see Chapter 4. This means that surgical removal of parts causes a defect in the final anatomy corresponding exactly to the fate map. Mosaic behavior is contrasted to regulative behavior and has nothing to do with genetic mosaics.

Screening for mutants b c d e Fig. In b and c genetic mosaics are made in which the red tissue is null mutant and the green tissue is wild type. In b spots appear in the wild-type zone so the gene must have an utonomous function corresponding, for example, to the wild-type expression pattern in d.

In c a spot appears in the zone of mutant tissue so the gene must have a nonautonomous function, corresponding, for example, to the expression pattern in e. The term forward genetics is sometimes used to describe investigations that start with the discovery of an interesting mutant phenotype.

Reverse genetics, by contrast, refers to functional investigations on a known gene. Many interesting mutants have arisen spontaneously, but even more have been recovered in large-scale screens on Drosophila, C. The details of these screens can be very complex, particularly for Drosophila in which there are many selective tricks for reducing the total number of individuals to be dealt with.

But the principle is simple and relies just on basic Mendelian genetics. The following description approximates to the procedures used in zebrafish screens, although is still slightly simplified Fig. A group of males will be mutagenized, for example by treatment with a chemical mutagen. This illustrates the simplest possible type of screen for zygotic recessives. Each F1 individual is outcrossed to generate a family at the F2 generation.

New findings in hot fields such as stem cells, regeneration, and aging should make it attractive to a wide readership. Overall, the book is concise, well structured, and illustrated. I can highly recommend it. This effort is no exception. Every student of developmental biology should experience his holistic yet analytical view of the subject.

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