Mechanisms of Development Flashcards
1
Q
Different animals use similar mechanisms and genes during development
A
- 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
2
Q
Genetic similarity in animals
A
- 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
3
Q
Homologous gene
A
- 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
4
Q
Model organisms in development
A
-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)
5
Q
Genome equivalence
A
- all cells contain the same set of genes
- the genetic material is identical in every cell, but different cells express different sets of genes
6
Q
Somatic nuclear transfer (cloning)
A
- 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
7
Q
Differential Gene Expression
A
- the concept: the genetic material is identical in every cell, but different cell types express different sets of genes
- gene regulatory protein
- regulatory modules
8
Q
Gene expression is regulated at several levels
A
- differential gene transcription (Enhancer and TFs)
- selective nuclear RNA processing
- selective mRNA translation
- differential protein modification
9
Q
RNA localization
A
- 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
10
Q
Differential gene expression controls fundamental cellular processes
A
- 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
11
Q
Induction
A
- 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
12
Q
Ectodermal competence
A
- 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
13
Q
Pax6
A
- 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
14
Q
Paracrine or juxtacrine signaling
A
- 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
15
Q
Morphogens
A
- 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
16
Q
Signaling Cascades
A
- 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
17
Q
Asymmetries along the left-right axis
A
- 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
18
Q
Left-right asymmetry defects
A
- 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
19
Q
Conserved asymmetric gene expression in vertebrate embryo
A
- 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
20
Q
Kartagener’s syndrome
A
- 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
21
Q
Asymmetric cilia-driven fluid flow in the node
A
- 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
22
Q
Nodal-Pitx2 signaling
A
- 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
23
Q
Examples of key mechanisms of development
A
- 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
