Animal Development: From Genes to Organism • Development Begins with Fertilization • Cleavage: Repackaging the Cytoplasm • Gastrulation: Producing the Body Plan • Neurulation: Initiating the Nervous System • Extraembryonic Membranes • Human Development
Development Begins with Fertilization • Fertilization is the union of a haploid sperm and egg to form a diploid zygote. • The entry of a sperm into an egg activates the egg metabolically and initiates the rapid series of divisions that produces the multicellular embryo. • In many species, the point of entry of the sperm creates an asymmetry in the radially symmetrical egg. • This asymmetry enables the bilateral body plan to emerge from the radial symmetry of the egg.
Development Begins with Fertilization • Nearly all the cytoplasm of the zygote is from the egg. • The egg cytoplasm is rich in nutrients, ribosomes, mitochondria, and mRNAs. • The sperm’s mitochondria degenerate, so all mitochondria in the zygote come from the egg. • In many species the sperm contributes a centriole, which becomes the centrosome of the zygote. • This produces the mitotic spindles for subsequent cell division.
Development Begins with Fertilization • In mammals, certain development genes are active only if they come from a sperm; others are active only if they come from an egg. • This phenomenon is called genomic imprinting. • Zygotes constructed in the laboratory with two male or two female nuclei fail to develop properly.
Development Begins with Fertilization • The entry of the sperm into the egg establishes the polarity of the embryo. • When cell division occurs, the cytoplasm of the zygote is not distributed equally among the daughter cells. • The uneven distribution of cytoplasmic elements results in signal transduction cascades that orchestrate the three steps of development: determination, differentiation, and morphogenesis.
Development Begins with Fertilization • In frogs, pigments in the egg cytoplasm allow easy study of development. • The dense nutrients accumulate in the vegetal hemisphere,which has no pigment. • The haploid nucleus of the egg is located in the animal hemisphere. The outermost (cortical) cytoplasm of this hemisphere is darkly pigmented. • Specific sperm-binding sites ensure that the sperm always enters the egg at the animal hemisphere. • After fertilization, the cortical cytoplasm rotates toward the site of sperm entry and exposes a less pigmented band opposite the point of sperm entry. This band is called the gray crescent.
Development Begins with Fertilization • Organelles and proteins move from the vegetal hemisphere to the gray crescent. • b-catenin, a transcription factor, and GSK-3, a protein kinase are found throughout the cytoplasm, but an inhibitor of GSK-3 is segregated in the vegetal pole. • After sperm entry, the inhibitor moves to the gray crescent and prevents degradation of b-catenin. • The concentration of b-catenin is higher on the dorsal side than on the ventral side of the embryo. • b-catenin is a key player in cell–cell signaling cascade that begins the process of determination.
Cleavage: Repackaging the Cytoplasm • Cleavage is the rapid series of mitotic cell divisions that follows fertilization. • In most animals, there is little cell growth or gene expression. • The embryo becomes a solid ball of small cells called a morula. • The ball eventually forms a fluid-filled cavity called a blastocoel, and the embryo is then called a blastula. The individual cells are blastomeres. • The pattern of cleavage is influenced by two factors: the amount of yolk and the formation of mitotic spindles.
Cleavage: Repackaging the Cytoplasm • Yolk is the nutrient material stored in an egg. Yolk impedes the formation of a cleavage furrow. • In embryos with little or no yolk, all daughter cells tend to be of similar size, as in the sea urchin.
Cleavage: Repackaging the Cytoplasm • When yolk quantity is larger, asymmetry of cell size is observed. • In the frog egg, the vegetal hemisphere ends up with fewer but larger cells than the animal hemisphere. • Both sea urchins and frogs have complete cleavage.
Cleavage: Repackaging the Cytoplasm • In eggs with a lot of yolk, such as the chicken egg, cleavage is incomplete. The cleavage furrows do not penetrate the yolk. • The embryo forms a disc of cells, called the blastodisc, on top of the yolk. • This type of incomplete cleavage is called discoidal cleavage and is common in birds, reptiles, and fish.
Cleavage: Repackaging the Cytoplasm • Another type of incomplete cleavage, called superficial cleavage, occurs in Drosophila and other insects. • The yolk is in the center of insect eggs. In early development, mitosis occurs but not cytokinesis. The nuclei migrate to the periphery of the egg, and the plasma membrane grows inward, partitioning the nuclei into individual cells.
Cleavage: Repackaging the Cytoplasm • Orientation of the mitotic spindles determine the cleavage planes and arrangements of daughter cells. • If the mitotic spindles form at right angles or parallel to the animal–vegetal axis, a radial cleavage pattern results. • If the mitotic spindles are at oblique angles to the animal–vegetal axis, the pattern has a twist, and is called spiral cleavage.
Cleavage: Repackaging the Cytoplasm • In mammals, the first cell division is parallel to the animal–vegetal axis and the second cell division occurs at right angles. • This pattern of cleaves is referred to as rotational cleavage and is unique to mammals. • Cleavage in mammals is slow, with divisions occurring 12 to 24 hours apart. • The cell divisions are not synchronous, so the number of cells in the embryo does not follow the regular progression (2, 4, 8, 16, 32, etc.) typical of other species.
Cleavage: Repackaging the Cytoplasm • Unlike other animals, gene expression plays a role during mammalian cleavage. • At the 8-cell stage of a mammal embryo, the cells form tight junctions and a compact mass. • At the transition from the 16-cell to 32-cell stage, the cells separate into two masses. • The inner cell mass develops into the embryo; the outer cells become the trophoblast, which becomes part of the placenta. • The trophoblast cells secrete fluid which forms the blastocoel. The embryo is called a blastocyst.
Cleavage: Repackaging the Cytoplasm • Fertilization in mammals occurs in the upper oviduct; cleavage occurs as the zygote travels down the oviduct. • When the blastocyst arrives in the uterus, the trophoblast adheres to the uterine wall (the endometrium), which begins the process of implantation. • Early implantation in the oviduct wall is prevented by the zona pellucida. • In the uterus, the blastocyst hatches out of the zona pellucida, and implantation can occur.
Cleavage: Repackaging the Cytoplasm • In all animals, cleavage results in the repackaging of the egg cytoplasm into the cells of the blastula. The cells get different amounts of nutrients and cytoplasmic determinants. • In the next stage, the cells of the blastula begin to move and differentiate. • The cells can be labeled with dyes to determine what tissues and organs develop from each. Fate maps of the blastula are the result.
Cleavage: Repackaging the Cytoplasm • Blastomeres become determined, or committed to a specific fate, at different times in different animals. • Roundworm and clam blastomeres are already determined at the 8-cell stage. • If one cell is removed, a portion of the embryo fails to develop normally. This is called mosaic development. • Other animals have regulative development. If some cells are lost during cleavage, other cells can compensate.
Cleavage: Repackaging the Cytoplasm • If blastomeres are separated in an early stage, two embryos can result. • Since the two embryos came from the same zygote, they are monozygotic twins, or genetically identical twins. • Non-identical twins are the result of two separate eggs fertilized by two separate sperm and are not genetically identical.
Gastrulation: Producing the Body Plan • Gastrulation is the process in which a blastula is transformed into an embryo with three tissue layers and body axes. • During gastrulation, three germ layers form: • The inner germ layer is the endoderm and gives rise to the digestive tract, circulatory tract, and respiratory tract. • The outer layer, the ectoderm, gives rise to the epidermis and nervous system. • The middle layer, the mesoderm, contributes to bone, muscle, liver, heart, and blood vessels.
Gastrulation: Producing the Body Plan • The sea urchin blastula is a simple, hollow ball of cells. • When gastrulation starts, the cells around the vegetal hemisphere flatten. The region invaginates into the blastocoel. • Some cells migrate away from the invaginating region and become primary mesenchyme cells. • The invagination becomes the primitive gut or archenteron, and the mesenchyme cells become mesododerm.
Gastrulation: Producing the Body Plan • Secondary mesenchyme cells break free from the tip of the archenteron. • The secondary mesenchyme cells are attached to the archenteron and send out extensions to the overlying ectoderm. The extensions contract, pulling the archenteron inward. • The region where the archenteron contacts the far side of the sphere becomes the mouth. • The anus forms at the region around the origin of the invagination, called the blastopore.
Gastrulation: Producing the Body Plan • Amphibian gastrulation begins when cells in the gray crescent change shape and bulge inward. These cells are called bottle cells. • The dorsal lip of the blastopore forms here. Successive sheets of cells move over the lip into the blastocoel in the process of involution. • The first cells form the archenteron. The following cells form the mesoderm. • Cells from the surface animal hemisphere migrate toward the blastopore, a process called epiboly. • Gastrulation is complete when three germ layers have been established.
Gastrulation: Producing the Body Plan • Experiments by Spemann and Mangold in the 1920s revealed much about amphibian development. • Spemann constricted salamander embryos with a single human baby hair. • Bisection with a shared gray crescent produced twins, but if just one side received a gray crescent, only that side developed. • Spemann hypothesized that cytoplasmic detrminants in the gray crescent are necessary for gastrulation.
Gastrulation: Producing the Body Plan • The next experiments involved transplanting gastrula tissues onto other gastrulas. • In transplants in early gastrulas, the transplanted pieces developed into tissue that were appropriate for the location where they were placed. The fates of the cells had not yet been determined. • If late gastrulas were used, the fates were determined, and transplants did not develop into the same tissue.
Gastrulation: Producing the Body Plan • Next, they transplanted the dorsal lip of the blastopore onto the belly area of another gastrula. • A second whole embryo developed. • Spemann and Mangold called the dorsal lip the primary embryonic organizer.
Gastrulation: Producing the Body Plan • The role of b-catenin in gastrulation has been verified using molecular biology technology. • When the production of b-catenin is depleted by injection of antisense RNA into the egg, no gastrulation proceeds. • If b-catenin is experimentally overexpressed in another region of the embryo, it can induce a second axis of embryo formation. • The protein b-catenin appears to play critical roles in generating signals that induce primary embryonic organizer activity.
Gastrulation: Producing the Body Plan • There are a number of known genes necessary for normal left–right organization of the body. • If one of these genes is knocked out, it can randomize the left–right organization of the internal organs. • The complete details of this mechanism are not fully known. • It appears that a left–right differential distribution of some of the of some of the transcription factors triggers a mechanism that acts very early during gastrulation.
Gastrulation: Producing the Body Plan • Bird and reptile embryos have modified gastrulation to adapt to huge yolk sizes. • Cleavage forms a blastodisc composed of an epiblast, which will form the embryo, and a hypoblast, which gives rise to the extraembryonic membranes. • The blastocoel is the fluid-filled space between the epiblast and the hypoblast.
Gastrulation: Producing the Body Plan • Gastrulation begins when cells move toward the midline of the epiblast, forming a ridge called the primitive streak. • A primitive groove forms along the primitive streak. • The primitive groove becomes the blastopore. Cells migrate through it and become endoderm and mesoderm. • At the forward region of the groove is Hensen’s node, which is equivalent to the dorsal lip of the amphibian blastopore. • Cells that pass over Hensen’s node become determined by the time they reach their destination.
Gastrulation: Producing the Body Plan • Mammal eggs have no yolk. • The inner cell mass of the blastocyst splits into an epiblast and hypoblast with a fluid-filled cavity in between. • The embryo forms from the epiblast; the extraembryonic membranes form from the hypoblast. • The epiblast also splits off a layer of cells that form the amnion. The amnion grows around the developing embryo. • Gastrulation is similar to that in birds; a primitive groove forms and cells migrate through it to become endoderm and mesoderm.
Neurulation: Initiating the Nervous System • Gastrulation produces an embryo with three germ layers. • Organogenesis occurs next and involves the formation of organs and organ systems. • Neurulation occurs early in organogenesis and begins the formation of the nervous system in vertebrates.
Neurulation: Initiating the Nervous System • The first cells to pass over the dorsal lip become the endodermal lining of the digestive tract. • The second group of cells become mesoderm. The dorsal mesoderm closest to the midline (chordomesoderm) becomes the notochord. • The notochord is connective tissue and is eventually replaced by the vetebral column. • The chordomesoderm induces the overlying ectoderm to begin forming the nervous system.