Mechanisms of Development

Question 1

Different animals use similar mechanisms and genes during development

Answer 1

• human, opossum, chicken, salamander, fish
• each of the vertebrate species shown here begins with a similar structures, but as they develop the species becomes less like each other
• similar genes and mechanisms have been found to control similar developmental processes in different animals

Question 2

Genetic similarity in animals

Answer 2

• 40% of human genes are present in flies and worms
• when genome sequencing has revealed that many human genes are found in invertebrates such as fruit flies and nematodes
• 92% of human genes are present in mice

Question 3

Homologous gene

Answer 3

• a gene similar in structure and evolutionary origin (and likely function) to a gene in another species
• in this example, a drosophilia protein produced artificially in a mouse embryo can perform the same function as the mouse version of the protein, successfully controlling the development of the architecture of the brain

Question 4

Model organisms in development

Answer 4

-due to similar mechanisms of development and homologous genes, researchers can use model organisms to study embryology under the premise that genes and mechanisms that control a specific aspect of development in one species are likely to play a similar role in the process in other species (including humans)

Question 5

Genome equivalence

Answer 5

• all cells contain the same set of genes

- the genetic material is identical in every cell, but different cells express different sets of genes

Question 6

Somatic nuclear transfer (cloning)

Answer 6

• provides evidence that all cells contain the same genes
• in 1997, Ian Wilmut cloned a sheep using somatic nuclear transfer from an adult female sheep
• a mammary gland cell nucleus from a donor was fused with an enucleated oocyte
• electrical pulses fused the egg and somatic cell and activated development. The resting blastocyst was implanted in a surrogate mother of a different breed of sheep, which gave birth to Dolly
• the nuclei of vertebrate adult somatic cells contain all of the genes necessary to generate an adult organism- no genes necessary for development have been lost: Donkey, Calf, Pig, Cat

Question 7

Differential Gene Expression

Answer 7

• the concept: the genetic material is identical in every cell, but different cell types express different sets of genes
• gene regulatory protein
• regulatory modules

Question 8

Gene expression is regulated at several levels

Answer 8

• differential gene transcription (Enhancer and TFs)
• selective nuclear RNA processing
• selective mRNA translation
• differential protein modification

Question 9

RNA localization

Answer 9

• RNA in situ hybridization is a technique used to detect mRNA expression in cells or tissues
• in this example, this specific mRNA is expressed only in the heart

Question 10

Differential gene expression controls fundamental cellular processes

Answer 10

• the expression of different sets of genes in different cells coordinates development by controlling four essential cellular processes by which the embryo is constructed
• cell proliferation: producing many cells from one
• cell specialization: creating cells with different characteristics at different positions
• cell interactions: coordinating the behavior of one cell with that of its neighbors
• cell movement: rearranging the cells to form structured tissues and organs

Question 11

Induction

Answer 11

• an interaction between different groups of cells
• one group changes the behavior of the other group (for example a change in cell shape, mitotic rate or cell fate)
• some inductive signals are short-range- notably those transmitted via cell- cell contracts; others are long-range, mediated by molecules that can diffuse through the extracellular medium
• inducer: the tissue that provides a signal that changes the behavior of the target tissue
• responder: the tissue being induced. The responder must have the ability to respond to the signal-referred to as competence

Question 12

Ectodermal competence

Answer 12

• classic example of induction: the optic vesicle is able to induce lens formation in the head ectoderm
• however, if the optic vesicle is placed in different location (e.g. trunk) that ectoderm will not form a lens
• only the head ectoderm is competent to respond to the signals from the optic vesicle
• if the optic vesicle is removed, the surface ectoderm fails to form a normal lens
• other tissues are not able to induce lens formation in the head ectoderm

Question 13

Pax6

Answer 13

• competence is actively acquired: Pax6 makes ectoderm competent to respond to inductive signals from the optic vesicle
• Pax6 transcription factor is important in providing competence to respond to the inducer signal from the optic cup

Question 14

Paracrine or juxtacrine signaling

Answer 14

• most of cell-cell communication include juxtacrine signaling and paracrine signaling
• paracrine factors are protein that are secreted into the extracellular space to deliver signals to neighboring cells
• juxtracrine- contact between the inducing and responding cells
• paracrine- diffusion of inducers from one cell to another

Question 15

Morphogens

Answer 15

• a paracrine signaling molecule secreted from a source that then acts directly on neighboring cells to produce specific responses that depend on concentration of the morphogen
• a morphogen can specify more than one cell type by forming a concentration gradient
• for example a high concentration may direct target cells into one developmental pathway, an intermediate concentration into another, and a low concentration into yet another
• morphogen gradients provide spatial information that subdivides a field of cells by inducing or maintaining the expression of different target genes at distinct concentration thresholds

Question 16

Signaling Cascades

Answer 16

• many inductive molecules and morphogens transmit their signals through the cell membrane and to the cell nucleus via signal transduction pathways
• the major signal transduction pathways are variation on a common theme
• signal receptor molecules positioned at the cell membrane first bind to the extracellular signaling molecule (the morphogen)
• this binding changes the conformation of the receptor
• this change often gives the receptor enzymatic activity (such as kinase activity to phosphophorylate itself other proteins) in the cell’s cytoplasm
• the active receptor kicks off a cascade of enzymatic (phosphorylation) processing of several intreacellular proteins, which ultimately activates a transcription factor in the nucleus that binds DNA and alters gene expression in the cell

Question 17

Asymmetries along the left-right axis

Answer 17

• the developmental processes involved in establishing the left-right body axis provides examples of the key concepts and mechanisms of embyo development we have discussed
• vertebrates look bilaterally symmetrical from the outside, but many of their internal organs- the heart, the stomach, the liver, the spleen- are asymmetric along the left-right axis

Question 18

Left-right asymmetry defects

Answer 18

• in contrast to the normal orientation of internal organs, known as situs solitus
• situs inversus totalis is a complete mirror-reversal of organ left- right asymmetry
• this condition has a low risk of malformations since all organs remain in concordant alignment
• in contrast, defects during embryogenesis that perturb left-right asymmetry of only a subset of organs cause a broad spectrum of congenital malformations that compromise organ function
• this situs ambiguous (also known as heterotaxy) occurs 1:10,000 live births and usually results in congenital malformations

Question 19

Conserved asymmetric gene expression in vertebrate embryo

Answer 19

• altered asymmetric gene expression correlates with altered organ asymmetry
• a key to the basis of left-right asymmetry comes from the discovery of asymmetric gene expression that precedes the first gross anatomical asymmetries
• the gene Nodal, coding for a member of the TGFb superfamily, is first expressed asymmetrically in the organizer/node region (in the mouse, chick, frog and zebrafish)
• this signal is then relayed to create a broad stripe of Nadal expression in the lateral plate mesoderm along the left side- and only the left side- of the embryos body
• this tightly regulated pattern is a good example of differential gene expression and shows that similar genes and mechanisms control similar developmental processes in different animals

Question 20

Kartagener’s syndrome

Answer 20

• triad: bronchiectasis, infertility, situs inversus (50%)
• a subset of infertile men were found to have sperm that were immotile because of a defect in molecules needed for beating of cilia and flagella
• these men also suffered from chronic bronchitis and sinusitis because the cilia in their respiratory tract were defective
• and strikingly, 50% of them had their internal organs left- right inverted, with the heart on the right
• together, these three symptoms are known as Kartagener’s syndrome
• this suggested that ciliary beating somehow controls which way the left-right axis is oriented

Question 21

Asymmetric cilia-driven fluid flow in the node

Answer 21

• cells at the node, on its internal face, have cilia that beat in a helical fashion to drive fluid towards the left side
• asymmetric fluid flow establishes a morphogen gradient that orients the left-right axis of the body
• cell-cell signaling cascade controls the relay of Nodal asymmetry, which depends on feedback loops involving Nodal together with a second set of genes, the Lefty genes, which act as Nodal antagonist
• another gene that is directly regulated by the Nodal pathway, Pitx2, links the outcome of the Nodal/Left interactions to subsequent anatomical development

Question 22

Nodal-Pitx2 signaling

Answer 22

• transfer of molecular left-right asymmetry to organs
• the transcription factor Pitx2 is expressed on the left side of the developing heart, gut and brain
• Pitx2 is thought to regulate expression of genes that mediate asymmetric morphogenesis of these organs

Question 23

Examples of key mechanisms of development

Answer 23

• cell-cell signaling cascade
• differential gene expression
• LR development is similar among vertebrates
• morphogen gradients: asymmetric flow
• the working model for how the left-right body axis is established during embryogenesis illustrates key concepts and mechanisms of development