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Flashcards in Mechanisms of Development Deck (23):
1

Different animals use similar mechanisms and genes during development

-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

Genetic similarity in animals

-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

Homologous gene

-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

Model organisms in development

-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

Genome equivalence

-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

Somatic nuclear transfer (cloning)

-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

Differential Gene Expression

-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

Gene expression is regulated at several levels

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

9

RNA localization

-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

Differential gene expression controls fundamental cellular processes

-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

Induction

-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

Ectodermal competence

-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

Pax6

-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

Paracrine or juxtacrine signaling

-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

Morphogens

-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

Signaling Cascades

-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

Asymmetries along the left-right axis

-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

Left-right asymmetry defects

-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

Conserved asymmetric gene expression in vertebrate embryo

-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

Kartagener's syndrome

-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

Asymmetric cilia-driven fluid flow in the node

-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

Nodal-Pitx2 signaling

-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

Examples of key mechanisms of development

-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