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Biology 624 - Developmental Genetics
Lecture #2 – Models and Concepts
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Developmental Behaviors
During development, cells do the following: --Divide --Move --Make adhesions with matrix and neighbors --Change shape --Differentiate*** --Activate and deactivate expression programs
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Developmental Hierarchy
Specification Determination Differentiation
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Specification The point when a cell will develop autonomously into a specific tissue or cell type in isolation.
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Field The total number of cells specified to form a specific cell type or tissue; i.e. all the cells of an embryo that have responded to an inducing signal.
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The ability of a group of cells to respond to an inducing signal.
Competence The ability of a group of cells to respond to an inducing signal.
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Determination The ability of a tissue to develop autonomously
irrespective of environment
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Cell Fate The normal developmental pathway a cell, or group of cells, will undergo during embryogenesis.
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Specification vs. Competence vs. Fate
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Differentiation Elaboration of a single cell type that is often, but not always, fixed from that time onward
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Potency The complete spectrum of cell types
and tissues that a cell can develop into IF exposed to the proper micro-environment Pluripotent vs Totipotent
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Lineage The developmental history or family tree reflecting the ancestry of a cell through out development
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Model Systems Worm (Caenorhabditis elegans) C. elegans
Fly (Drosophila melanogaster) Drosophila Fish (Danio rerio) Zebrafish Frog (Xenopus laevis and Xenopus tropicalis) Chick (Gallus gallus) Mouse (Mus Musculus domesticus)
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Other Model Systems Slime Molds Tunicates/Sea squirts/Ascidians
Sea urchin Molluscs Plants Human
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* * * * * * 16h 0h 6h 1.5h 0h 10h 2.5h 24h 18h 3.5h 36h 5h 2.8h 24h
cleavage GASTRULATION organogenesis 0h 10h 2.5h 24h cleavage GASTRULATION organogenesis * dorsal closure 18h 3.5h cleavage GASTRULATION neurulation * organogenesis 36h 5h 2.8h cleavage GASTRULATION segmentation * organogenesis 24h 48-72h 10h 4d 24h cleavage GASTRULATION segmentation * organogenesis 7d 21d 4.5d 24h first cleavage GASTRULATION segmentation * organogenesis 6.5d 20d 14d implantation
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Caenorhabditis elegans
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Caenorhabditis elegans (3 Days)
Small number of cells Simple anatomy Few genes (approx. 2000) Relatively fixed lineage -all relationships known Genetics and RNAi
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C. elegans embryogenesis
16h 0h 6h 1.5h cleavage GASTRULATION organogenesis * Figures\Chapter08\DevBio7e08420.jpg
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Caenorhabditis elegans
Hallmarks of Development Self Fertilization (only males or hermaphrodites) Fixed cell lineages After hatching close resemblance to adult except lacks gonadal structures 4 molts Embryos transparent Genetics and RNAi feeding
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Drosophila melanogaster
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Drosophila melanogaster (12 Days)
Genetics Mosaics Polytene Chromosomes Homologous Recombination
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Drosophila embryogenesis
cleavage GASTRULATION organogenesis * dorsal closure Figures\Chapter08\DevBio7e08420.jpg
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Drosophila melanogaster
Hallmarks of Development Develops as syncytium for first 9 divisions; i.e. molecules are free to diffuse across embryo. Gastrulates at 3 hours Germ band extension Cells set aside after gastrulation as discrete units, Imaginal Discs, that will give rise to specific adult organs after morphogenesis 3 molts Develops as “upside down vertebrate”, e.g. nervous system on ventral portion of embryo, heart on ventral side
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Drosophila melanogaster
Hallmarks of Development Develops as syncytium for first 9 divisions; i.e. molecules are free to diffuse across embryo. Gastrulates at 3 hours Germ band extension Cells set aside after gastrulation as discrete units, Imaginal Discs, that will give rise to specific adult organs after morphogenesis 3 molts Develops as “upside down vertebrate”. Nervous system on ventral portion of embryo.
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Drosophila melanogaster
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Drosophila melanogaster
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Drosophila melanogaster
Hallmarks of Development Develops as syncytium for first 9 divisions; i.e. molecules are free to diffuse across embryo. Gastrulates at 3 hours Germ band extension Cells set aside after gastrulation as discrete units, Imaginal Discs, that will give rise to specific adult organs after morphogenesis 3 molts Develops as “upside down vertebrate”. Nervous system on ventral portion of embryo.
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Drosophila melanogaster
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Xenopus laevis (Xenopus tropicalis)
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18h 3.5h * 36h Frog embryogenesis cleavage GASTRULATION neurulation
Figures\Chapter08\DevBio7e08420.jpg 18h 3.5h cleavage GASTRULATION neurulation * organogenesis 36h
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Xenopus laevis (Xenopus tropicalis)
Hallmarks of development High Fecundity; large embryos Early development under maternal control No cell mixing Good fate map via direct manipulation Concepts of specification, determination etc. Gastrulation well-studied Explants (e.g. animal caps) can be cultured in simple salt solutions MOs work well for gene knockdown
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Metamorphosis
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Brachydanio rerio
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Brachydanio rerio (12 weeks)
Short life cycle Transparent High Fecundity Relative ease of tissue transplantation Genome has gone through a relatively recent duplication
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Zebrafish embryogenesis
cleavage GASTRULATION segmentation * organogenesis 24h 48-72h 10h
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Brachydanio rerio Hallmarks of development High Fecundity
Embryos transparent and develop in sea water Transgenesis; reporter lines; inducible gene expression; MOs Development similar to frog but better genetics
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Gallus gallus
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Gallus gallus (3 months)
100s of chromosomes; genetics poor Generation time (fertilization to fertilization) long – up to a year; thus genetics poor Historical (remember Aristotle!)
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4d 24h * 7d 21d Chick embryogenesis Egg laid cleavage GASTRULATION
segmentation * organogenesis 7d 21d Egg laid
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Gallus gallus Hallmarks of development
Embryo develops outside mother (in ovo) and accessible for manipulations Develops as a disc Genes can be introduced by electroporation or retrovirus Early development similar to mouse Trace the fate of a group of cells in chick-quail chimera (or quail-mouse chimera)
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Mus Musculus domesticus
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Mus Musculus domesticus (42 days)
Mammal Genetics ES cells Homologous Recombination Transgenics
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Mus Musculus domesticus
Hallmarks of development Implants in mother Extra -embryonic tissue (placental connection to mom) Compaction Turning Gastrulation associated with proliferation
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4.5d 24h * 6.5d 20d 14d Mouse embryogenesis first cleavage
GASTRULATION segmentation * organogenesis 6.5d 20d 14d implantation
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Mus Musculus domesticus
Hallmarks of development Implants in mother Extra-embryonic tissue (placental connection to mom) Compaction Turning Historical (remember Salome!) genetics Amenable to transgenesis; knockouts; conditional knockouts; reporter lines
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