Developmental Biology. Cell Fate, Potency, and Determination
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1 Developmental Biology Cell Fate, Potency, and Determination
2 Definitions Fate The sum of all structures that the cell or its descendants will form at a later stage of normal development.
3 Cell Fate & Fate Maps Figure 1.10 Figure 6.2
4 Fate Maps intraspecific Figure 10.26
5 Fate Maps interspecific Nature Reviews Neuroscience 2, (2001); doi: / CUTTING, PASTING AND PAINTING: EXPERIMENTAL EMBRYOLOGY AND NEURAL DEVELOPMENT
6 2 cell Methods fate mapping fluorescent dye macromolecules e.g. dextran RNA 2 cell trophoblast & inner cell mass Figure 6.3 zebrafish embryo 32 cell mouse embryo
7 Methods fate mapping Isolation Heterotopic transplantation Clonal analysis
8 Methods Clonal analysis Somatic cross over is induced in heterozygous cells by X ray exposure: some cells will become homozygous for a certain alleles (e.g. cuticle color, bristle type) surviving cell clones deriving from this founder cell can be recognized in later stages of development compartments Fig 6.m1 Figure 6.4
9 Definitions Fate The sum of all structures that the cell or its descendants will form at a later stage of normal development. Potency The total of all structures that a cell can form in an appropriate environment. Totipotent cell or region can give rise to complete individual Pluripotent cell or region can form more structures than their fate
10 Pluripotency (lack of determination) demonstrated by clonal analysis labeled cell determined not determined Fate Figure 6.5
11 Methods blastomere isolation to test potency
12 Definitions Fate The sum of all structures that the cell or its descendants will form at a later stage of normal development. Potency The total of all structures that a cell can form in an appropriate environment. Determination A stepwise process during which the potency of cell becomes limited to its fate.
13 Isolation experiment showing bias (Drosophila gastrula) cells in this region form epidermis cells in this region form neurons ~ ½ the time and epidermis the other ½
14 Isolation Experiment Demonstration of Bias DEA epidermis VNR ½ neural; ½ epidermis Figure 6.7 DEA Isolated cells: DEA cells form epidermis cells in accord with fate isolated cells VNR cells only form neural cells, NO epidermis not in accord with fate Conclusion: VNR cells are biased towards forming neural cells, but can be influenced toward forming epidermis. VNR neural neur/epid epidermal Figure 6.8
15 Determination and Bias Transplantation Experiment homotopic transplants clones formed in accord with fate heterotopic transplants: DEA VNR = groups of cells = original fate single cells = new fate } community effect VNR DEA = neural & epidermal (in accord with fate) VNR PNR/Proct = neural (not in accord with fate)
16 Mechanisms for modifiying bias Community effect exchange of signals among equivalent cells; stabilizes same determined state for all of them Lateral inhibition equivalent cells compete to attain a preferred state; one cell inhibits neighbors from attaining same fate e.g. Notch/Delta (Drosophila)
17 Mechanisms for modifiying bias Community effect exchange of signals among equivalent cells; stabilizes same determined state for all of them Lateral inhibition equivalent cells compete to attain a preferred state; one cell inhibits neighbors from attaining same fate Induction interaction between nonequivalent cells
18 Embryonic Induction Induction induction
19 Properties of the determined state Determination is assessed by operational criteria. e.g. results of isolation & transplantation experiments NOT biochemical or morphological characteristics Determination is a stepwise process; negative and positive steps. loss of potency (potential) + instruction Hierarchy of determinative events
20 Stepwise determination hierarchy of determinative events determinative steps Figure 6.16
21 Properties of the determined state Determination is assessed by operational criteria. e.g. results of isolation & transplantation experiments NOT biochemical or morphological characteristics Determination is a stepwise process; negative and positive steps. loss of potency (potential) + instruction Hierarchy of determinative events Localized cytoplasmic determinants establish patterns. e.g. insect pole plasm induces primordial germ cells (pole cells) Determined state is stably (mostly) passed on during mitosis. genetic and epigenetic controls
22 Regulation in Development invariant cleavage (e.g. C. elegans) precise harmony (timing and fate) during development
23 C. elegans invariant development Figure 1.12
24 Regulation in Development invariant cleavage (e.g. C. elegans) precise harmony (timing and fate) during development variable cleavage (most species) use stepwise approximation to correct imbalances development in individual cells can be shifted mosaic development (nematodes, ascidians) potency map is identical to fate map all cells determined regulative development (amphibian, sea urchin, mammals) potency greater than fate cells not yet determined
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