1. Biology 624 - Developmental Genetics
Lecture #2 – Models and Concepts

2. Developmental Behaviors
During development, cells do the following:
--Divide
--Move
--Make adhesions with matrix and neighbors
--Change shape
--Differentiate***
--Activate and deactivate expression programs

3. Developmental Hierarchy
Specification
Determination
Differentiation

4. Specification
The point when a cell will develop autonomously into a specific tissue or cell type in isolation.

5. 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.

6. 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.

7. Determination The ability of a tissue to develop autonomously
irrespective of environment

8. Cell Fate
The normal developmental pathway a cell, or group of cells, will undergo during embryogenesis.

9. Specification vs. Competence vs. Fate

10. Differentiation
Elaboration of a single cell type that is often, but not always, fixed from that time onward

11. 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

12. Lineage
The developmental history or family tree reflecting the ancestry of a cell through out development

13. 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)

14. Other Model Systems Slime Molds Tunicates/Sea squirts/Ascidians
Sea urchin
Molluscs
Plants
Human

15. * * * * * * 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

16. Caenorhabditis elegans

17. Caenorhabditis elegans (3 Days)
Small number of cells
Simple anatomy
Few genes (approx. 2000)
Relatively fixed lineage -all relationships known
Genetics and RNAi

18. C. elegans embryogenesis
16h 0h 6h
1.5h
cleavage
GASTRULATION
organogenesis *
Figures\Chapter08\DevBio7e08420.jpg

19. 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

20. Drosophila melanogaster

21. Drosophila melanogaster (12 Days)
Genetics
Mosaics
Polytene Chromosomes
Homologous Recombination

22. Drosophila embryogenesis
cleavage
GASTRULATION
organogenesis *
dorsal closure
Figures\Chapter08\DevBio7e08420.jpg

23. 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

24. 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.

25. Drosophila melanogaster

26. Drosophila melanogaster

27. 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.

28. Drosophila melanogaster

29. Xenopus laevis (Xenopus tropicalis)

30. 18h 3.5h * 36h Frog embryogenesis cleavage GASTRULATION neurulation
Figures\Chapter08\DevBio7e08420.jpg
18h
3.5h
cleavage
GASTRULATION
neurulation *
organogenesis
36h

31. 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

32. Metamorphosis

33. Brachydanio rerio

34. Brachydanio rerio (12 weeks)
Short life cycle
Transparent
High Fecundity
Relative ease of tissue transplantation
Genome has gone through a relatively
recent duplication

35. Zebrafish embryogenesis
cleavage
GASTRULATION
segmentation *
organogenesis
24h
48-72h
10h

36. 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

37. Gallus gallus

38. 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!)

39. 4d 24h * 7d 21d Chick embryogenesis Egg laid cleavage GASTRULATION
segmentation *
organogenesis 7d
21d
Egg laid

40. 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)

41. Mus Musculus domesticus

42. Mus Musculus domesticus (42 days)
Mammal
Genetics
ES cells
Homologous Recombination
Transgenics

43. Mus Musculus domesticus
Hallmarks of development
Implants in mother
Extra -embryonic tissue (placental connection to mom)
Compaction
Turning
Gastrulation associated with proliferation

44. 4.5d 24h * 6.5d 20d 14d Mouse embryogenesis first cleavage
GASTRULATION
segmentation *
organogenesis
6.5d
20d
14d
implantation

45. 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