Transcript Drosophila melanogaster

Biology 624 - Developmental Genetics
Lecture #2 – Models and Concepts
Developmental Behaviors
During development, cells do the following:
--Divide
--Move
--Make adhesions with matrix and neighbors
--Change shape
--Differentiate***
--Activate and deactivate expression programs
Developmental
Hierarchy
1. Specification
2. Determination
3. Differentiation
Specification
The point when a cell will develop
autonomously into a specific tissue or
cell type in isolation.
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.
Competence
The ability of a group of cells to respond to an
inducing signal.
Determination
The ability of a tissue to develop autonomously
irrespective of environment
Cell Fate
The normal developmental pathway a
cell, or group of cells, will undergo
during embryogenesis.
Specification vs.
Competence vs. Fate
Differentiation
Elaboration of a single cell type that is
often, but not always, fixed from that time
onward
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
Lineage
The developmental history or family tree
reflecting the ancestry of a cell through
out development
Model Systems
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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)
Other Model Systems
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Slime Molds
Tunicates/Sea squirts/Ascidians
Sea urchin
Molluscs
Plants
Human
cleavage
*
1.5h
0h
organogenesis
GASTRULATION
16h
6h
*
organogenesis
cleavage GASTRULATION
2.5h
0h
cleavage
2.8h
24h
10h
cleavage
3.5h
dorsal closure
*GASTRULATION
neurulation organogenesis
36h
18h
*
GASTRULATION
segmentation
5h
10h
organogenesis
24h
48-72h
*
GASTRULATION
cleavage
organogenesis
segmentation
24h
first cleavage
24h
4d
21d
7d
*
implantation GASTRULATION
organogenesis
4.5d
6.5d
segmentation
14d
20d
Caenorhabditis elegans
Caenorhabditis elegans
(3 Days)
 Small number of cells
 Simple anatomy
 Few genes (approx. 2000)
 Relatively fixed lineage -all relationships known
 Genetics and RNAi
C. elegans embryogenesis
cleavage
0h
* GASTRULATION
1.5h
6h
organogenesis
16h
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
Drosophila melanogaster
Drosophila melanogaster
(12 Days)
Genetics
Mosaics
Polytene Chromosomes
Homologous Recombination
Drosophila embryogenesis
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organogenesis
cleavage GASTRULATION
0h 2.5h
dorsal closure
10h
24h
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
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.
Drosophila melanogaster
Drosophila melanogaster
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.
Drosophila melanogaster
Xenopus laevis
(Xenopus tropicalis)
Frog embryogenesis
* GASTRULATION
3.5h 18h
cleavage
neurulation
organogenesis
36h
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
Metamorphosis
Brachydanio rerio
Brachydanio rerio
(12 weeks)
 Short life cycle
 Transparent
 High Fecundity
 Relative ease of tissue transplantation
 Genome has gone through a relatively
recent duplication
Zebrafish embryogenesis
* GASTRULATION segmentation
2.8h 5h
10h 24h
cleavage
organogenesis
48-72h
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
Gallus gallus
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!)
Chick embryogenesis
Egg laid
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GASTRULATION
cleavage
organogenesis
24h
segmentation
4d
7d
21d
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 chickquail chimera (or quail-mouse chimera)
Mus Musculus domesticus
Mus Musculus domesticus
(42 days)
Mammal
Genetics
ES cells
Homologous Recombination
Transgenics
Mus Musculus domesticus
Hallmarks of development
 Implants in mother
 Extra -embryonic tissue (placental connection to
mom)
 Compaction
 Turning
 Gastrulation associated with proliferation
Mouse embryogenesis
first cleavage
24h
implantation
4.5d
* GASTRULATION
organogenesis
6.5d
segmentation
14d
20d
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