1. 4061 Molecular and Cellular Principles of Animal Development

2. 4061 Molecular and Cellular Principles of Animal Development
Classic approaches to embryonic development
Molecular approach- genes take centre stage ‘genetic programs underlying development’
‘Programs executed by molecular networks of proteins operating within and between cells’
‘In order to understand development we need to understand the underlying genetic circuitry’
‘Moving from an organism-based approach towards molecular mechanisms’

3. Primary Question
How can a complex animal emerge from a single egg?
Fourth century BC Aristotle dissected chicken’s eggs
Principle of ‘epigenesis’- development a process of growth in size combined with increasing complexity and organization
Descriptive Embryology
Development of microscope in seventeenth century
Experimental Embryology
Wilhelm Roux- ‘empirical approach
Manipulate frog embryo and observe consequences ‘embryonic induction’

4. Developmental Genetics (70’s)
Drosophila melanogaster – transmission of genetic traits
Genetics meets Molecular Biology
Clone the developmental genes
Developmental Biology
Fusion of Molecular Biology, genetics and morphology

5. Impact on Society
In vitro fertilization (IVF)
‘Teratology’ effect of environmental agents (chemicals, viruses, radiation) on embryos
Chromosomal basis of some human birth defects (amniocentesis)
Future
Functional genomics - therapeutic targets
- combinatorial chemistry
Tissue repair - Stem cells
- ex vivo tissue engineering
- organogenesis
Genetic engineering - ‘cloning’!!!

6. Readings from Gilbert 11th edition
Chapter p1-27 Mechanisms of Developmental Organization(p1-27 ( 10th p5-29) Comprehending Development
- intro read for general interest
Chapter 3 Differential Gene Expression p (Ch 2 p th)

7. The essence of embryonic development:
A regulated expansion in cell numbers, co-ordinated in space and time with an increase in cell diversity

8. Primary Question How can a complex animal emerge from a single egg?
Questions of Differentiation
Questions of morphogenesis
Questions of growth
Questions of regeneration
Questions of evolution
Questions of environmental adaptation

9. SC/BIOL 4061,SC/BCHM 4061 Molecular and Cellular Principles of Animal Development Winter term, 2017 OUTLINE
Course Director: John McDermott PhD
Office : 427b  Life Sciences Building
Office tel extension: 30344
address:
Web site:      
Scheduled Office hours: TBA ( for an appointment or to request an alternate time to meet)
Topic outline
1)                  Introduction to Molecular Analysis of Development -Descriptive embryology -Genetics and molecular biology
2)                  Programs and Regulatory Elements in DNA
3)                  Transcriptional Circuits- epigenetic regulation of gene expression- differential gene expression
4)                  Gastrulation and early development- axis specification and formation
5)                  Features of Major Model Organisms- Mouse, Chick, Drosophila
6)                  Techniques for the study of Mouse Development: gene targeting/editing technology
7)                  Receptors, Ligands
8)                  Cell-cell communication, Signaling Networks, Induction and Competence
9)                  Molecular Co-ordination of Cell Division and Differentiation ( Myogenesis)
10)              Focus on Paraxial Mesoderm, Somitogenesis and Patterning

10. 1 Essay (HARD COPY due date Tue 28th March by 5pm ) 30%
11)              Cell  Death in Development
12)              Lineage Generation - Embryonic and Adult Stem cell properties and lineage commitment
13)              Cell Type Specification, Induction of pluripotency in stem cells (iPS) and cell fate programming
14)              Patterning in 1 and 2 Dimensions
15)              Molecular and cellular basis of 3D Patterning- Heart development
16)              Postembryonic development:  Regeneration and Aging
17)             Developmental mechanisms of evolutionary conservation and change
Evaluation
1 Test (prior to Reading week -date: Thurs 16th Feb) 30%
1 Essay (HARD COPY due date Tue 28th March by 5pm ) 30%
(In some cases students may be able to do a class presentation
in lieu of the essay assignment on permission of the instructor)
1 Test (Final in exam period date -TBA) 40%    
Course Text: (11th edition available in York bookstore)
Developmental Biology
Companion web site: 
Scott F.Gilbert
Sinauer Associates, Inc
ISBN

11. ZYGOTE
CLEAVAGE
GASTRULATION
ectoderm
endoderm
mesoderm

12. 4061

13. Comparative embryology
snake
tortoise
chicken
dolphin
monkey
Ernst Haeckel (4 edn 1903)

15. The development of animal model systems.
Nematode C.elegans

16. The development of animal model systems
Fruit fly Drosophila melanogaster P A D

17. The development of animal model systems, cont’d
Frog Xenopus laevis

18. The development of animal model systems, cont’d
Zebrafish

19. The development of animal model systems, cont’d
Chick

20. The development of animal model systems, cont’d
Mouse

21. Types of evidence Correlative- weakest Loss of function
Gain of function

22. A few classical terms concerning cell migration during gastrulation

23. Programs and regulatory elements in DNA and RNA
Gilbert, Chapter 3 p45-93 Differential Gene Transcription

24. DNA content and number of genes
21,733
17,000
24,189
21,000

25. DNA content and number of genes, cont’d Phylogenetic analysis

26. Fundamental principles of development at the cellular level:
Cell proliferation
Continuous but regulated increase in cell diversity

28. General pattern of regulatory sequences

29. Model for assembly of the RNA polymerase II initiation complex on a TATA-containing promoter

31. GENE mRNA TF Gene A (on) Gene B (on) Gene C (off) Gene D (on) mRNA5` 3` TF
Gene A (on)
Gene B (on)
Gene C (off)
Gene D (on)
mRNA
mRNA
mRNA
Protein A
Protein B
Protein D

32. Regulation of Transcription Factors
Homeodomain Engrailed
Zinc Finger ZIF 268
Zinc Finger Gluc. Receptor
Ribbon

33. Leucine Zipper GCN 4
HLH-leucine zipper MAX
GCN 4:DNA

34. Modular design of eukaryotic transcription factors
DNA b.d.
Act.d N C
Transcription factor x
CANNTG
unrelated protein
tgacgtca

35. Control of CREB activity by cAMP
OFF ON
Ser 133
Nucleus C R +
cAMP
PKA holoenzyme
PKA catalytic subunit

36. Regulation of NFkB activity
p65
p50 I P
Nucleus

37. Fig 2.8 Fusion of reporter genes to the enhancer region
13.5d Myf 5 LacZ reporter expressed in eye,
facial limb muscles and segmented myotome
GFP fused to a lens crystallin promoter in
Xenopus tropicalis

38. Epigenetic control of gene expression
devbio8e-fig jpg

39. Nucleosome and chromatin structure
devbio8e-fig jpg

40. 5.10 TAFII250, a TAF that binds TBP, can function as a histone acetyltransferase
devbio8e-fig jpg

41. DevBio9e-Fig R.jpg

42. Cell Signalling Protein RNA DNA
What regulates the transcription factors ?
Cell Signalling
modification
Protein
functional protein interacting with other proteins
RNA
DNA

43. Overview of RNA processing in eukaryotes using β-globin genes

44. Alternative Splicing E1 E3 E2 I1 I2
gene
RNA1
mRNA1
mRNA2
RNA2

45. Alternative Splicing E1 E3 E2 I1 I2
gene
RNA1
mRNA1
mRNA2
RNA2