1. Animal Development: From Genes to Organism

2. 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

3. 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.

4. 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.

5. Figure 20.1 Sperm and Egg Differ Greatly in Size

6. 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.

7. 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.

8. 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.

9. Figure 20.2 The Gray Crescent

10. 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.

11. Figure 20.3 Cytoplasmic Factors Set Up Signaling Cascades

12. 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.

13. 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.

14. Figure 20.4 Patterns of Cleavage in Four Model Organisms (Part 1)

15. 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.

16. 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.

17. Figure 20.4 Patterns of Cleavage in Four Model Organisms (Part 2)

18. 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.

19. 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.

20. 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.

21. Figure 20.5 The Mammalian Zygote Becomes a Blastocyst (Part 1)

22. Figure 20.5 The Mammalian Zygote Becomes a Blastocyst (Part 2)

23. 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.

24. 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.

25. 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.

26. Figure 20.6 Fate Map of a Frog Blastula

27. 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.

28. 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.

29. Figure 20.7 Twinning in Humans

30. 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.

31. 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.

32. 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.

33. Figure 20.8 Gastrulation in Sea Urchins

34. 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.

35. Figure 20.9 Gastrulation in the Frog Embryo (Part 1)

36. Figure 20.9 Gastrulation in the Frog Embryo (Part 2)

37. Figure 20.9 Gastrulation in the Frog Embryo (Part 3)

38. 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.

39. Figure 20.10 Spemann’s Experiment

40. 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.

41. 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.

42. Figure 20.11 The Dorsal Lip Induces Embryonic Organization

43. 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.

44. Figure 20.12 Molecular Mechanisms of the Primary Embryonic Organizer

45. 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.

46. 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.

47. Figure 20.13 Gastrulation in Birds (Part 1)

48. 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.

49. Figure 20.13 Gastrulation in Birds (Part 2)

50. 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.

51. 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.

52. 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.

53. Neurulation: Initiating the Nervous System
Neurulation begins with thickening of the ectoderm above the notochord to form the neural plate.
Edges of the neural plate thicken to form ridges. Between the ridges a grove forms and deepens.
The ridges fuse, forming a cylinder—the neural tube.
The anterior end of the neural tube becomes the brain.

54. Figure 20.15 Neurulation in the Frog Embryo (Part 1)

55. Figure 20.15 Neurulation in the Frog Embryo (Part 2)

56. Neurulation: Initiating the Nervous System
In humans, failure of the neural tube to close completely at the posterior end results in spina bifida.
If the tube fails to close at the anterior end, the result is anencephaly, in which the forebrain does not develop.
Neural tube defects can be reduced if pregnant women receive adequate folic acid (a B vitamin).

57. Neurulation: Initiating the Nervous System
Body segmentation develops during neurulation.
Blocks of mesoderm called somites form on both sides of the neural tube.
Somites produce cells that form the vertebrae, ribs, and muscles of the trunk and limbs. They also guide the organization of the peripheral nerves.
When the neural tube closes, cells called neural crest cells break loose; they migrate inward between the epidermis and the somites and under the somites.
The neural crest cells give rise to many structures, including peripheral nerves, which connect to the spinal cord.

58. Figure 20.16 The Development of Body Segmentation

59. Neurulation: Initiating the Nervous System
As development progresses, the body segments differentiate.
Differentiation on the anterior–posterior axis is controlled by homeotic genes.
Four families of genes, called homeobox or Hox genes, control differentiation along the body axis in mice.
Each family consists of 10 genes and resides on a different chromosome.
Temporal and spatial expression of these genes follows the same pattern as their linear order on their chromosomes.

60. Figure 20.17 Hox Genes Control Body Segmentation (Part 1)

61. Figure 20.17 Hox Genes Control Body Segmentation (Part 2)

62. Neurulation: Initiating the Nervous System
Other genes give dorsal–ventral position information.
Sonic hedgehog is an example of a dorsal–ventral gene that is expressed in the notochord and induces cells in the overlying neural tube to become ventral spinal cord cells.
Another family of homeobox genes, the Pax genes, are important in nervous system and somite development.
Pax3 is expressed in neural tube cells that will become dorsal spinal cord cells.
Pax3 and sonic hedgehog interact to determine dorsal–ventral differentiation of the spinal cord.

63. Extraembryonic Membranes
Extraembryonic membranes originate from the germ layers of the embryo and function in nutrition, gas exchange, and waste removal.
In the chicken, the yolk sac is the first to form, by extension of the endodermal tissue of the hypoblast.
It constricts at the top to create a tube that is continuous with the gut of the embryo.
Yolk is digested by the endodermal cells of the yolk sac, and the nutrients are transported through blood vessels lining the outer surface of the yolk sac.

64. Extraembryonic Membranes
The allantoic membrane, an outgrowth of the extraembryonic ectoderm, forms the allantois, a sac for storage of metabolic wastes.
Ectoderm and mesoderm combine and extend beyond the embryo to form the amnion and the chorion.
The amnion surrounds the embryo, forming a cavity. The amnion secretes fluid into the cavity that provides protection for the embryo.
The chorion form a continous membrane just under the eggshell. It limits water loss and functions in gas exchange.

65. Figure 20.18 The Extraembryonic Membranes

66. Extraembryonic Membranes
In mammals, the first extraembryonic membrane to form is the trophoblast.
When the blastocyst hatches from the zona pellucida, the trophoblast cells attach to the uterine wall, This is the beginning of implantation.
The trophoblast becomes part of the uterine wall, and sends out villi to increase surface area and contact with maternal blood.
The hypoblast cells extend to form the chorion. The chorion and other tissues produce the placenta.
The epiblast produces the amnion. Allantoic tissues form the umbilical cord.

67. Figure 20.19 The Mammalian Placenta

68. Extraembryonic Membranes
Cells from the embryo that are in the amniotic fluid can be sampled and tested for defects. The test is called amniocentesis.
Problems such as Down syndrome, cystic fibrosis, and Tay Sachs disease can be detected using this technique.
A newer technique is chorionic villus sampling which makes earlier detection possible.

69. Figure 20.20 Chorionic Villus Sampling

70. Human Development
The events of human gestation (pregnancy) are divided into three trimesters.
The first trimester begins with fertilization. Implantation takes place 6 days later.
Then gastrulation takes place, the placenta forms, and tissues and organs begin to form.
The heart first beats at 4 weeks and limbs form at 8 weeks.
The embryo is particularly vulnerable to radiation, drugs, and chemicals during the first trimester.
Hormonal changes can cause major responses in the mother, including morning sickness.

71. Human Development
During the second trimester the fetus grows rapidly to about 600g.
Fingers, toes, and facial features become well formed.
Fetal movements are first felt by the mother early in the second trimester.
By the end of the second trimester, the fetus may suck its thumb.

72. Human Development
The fetus and the mother continue to grow during the third trimester.
Throughout the third trimester, the fetus remains susceptible to environmental factors such as malnutrition, alcohol consumption, and cigarette smoking.
Kidneys produce urine, the liver stores glycogen, and the brain undergoes cycles of sleep and waking.

73. Figure 20.21 Stages of Human Development

74. Human Development
Development does not end at birth.
The organization of the nervous system exhibits a great deal of plasticity in the early years, as patterns of connections between neurons develop.
For example, a child born with misaligned eyes will use mostly one eye.
The connections to the brain from this eye will become stronger, while the connections to the other eye will become weak.
This can be changed if the alignment is corrected within the first three years.

75. Human Development
A current area of research into this developmental plasticity in the nervous system examines the role of learning in stimulating the production and differentiation of new neurons in the brain.