Developmental Biology
MCDB 4650 – Fall 2023

DEVO@CU provides an introduction to key observations, principes, methods, and systems used to study socio-cellular interactions & developing systems

WEEK 1 – Tuesday 29 August

1. How the course works & what you can expect – reviewing ideas we will be using, repeatedly  + signing up & using beSocratic

→ slides also posted on nota bene - NB tutorial

optional: Hossenfelder Heisenberg's microscope

 →worth watching: Feynmann Understanding magnetic attraction

on nota bene and down-loadable here: pre-Devo refresher
Making mechanistic sense

optional stuff: How would Socrates teach science?
+ The surprising conservation of cellular processe

Thursday 31 August

2. Reviewing molecluar & cellular level basics – lessons from the lac operon (noise)  → slides

optional : Coping with the noisy nature of life

review beSocratic 1

Portfolio questions:
2.1 What are the sources of noise in the lac operon (and other biological systems)?
2.2 How might changes in gene expression become (effectively) irreversible?
2.3 How is that cells with the same genotype develop different phenotypes?

WEEK 2 – Tuesday 5 September

3. Some technological caveats +  Signaling systems, gradients, thresholds, and modeling – lessons from Saka & Smith   → slides

review beSocratic 2

Portfolio questions:
3.1 What are the common features of signaling systems?
3.2 Why are dose-response curves typically sigmoidal, not linear?
3.3 How might the response to a signal lead to cells that are unresponssive to that signal?

Thursday 7 September

4. Origins of cellular asymmetries and differences (e.g. Caulobacter)  → slides

review beSocratic 3

Portfolio questions:
4.1 How might asymmetries arise at the cellular level?
4.2 How can one DNA strand be older than the other? how might impact cell behavior?
4.3 Where might the handedness of a cell / organism come from?

WEEK 3 – Tuesday 12 September

5.Social systems, quorum sensing & transient metazoans: decision making & differentiation – Dictyostelium

→ slides    after class zoom video

review beSocratic 4

Portfolio questions:
5.1 How is quorum sensing used by unicellular organisms?
5.2 In a transient (social) metaozoan, why would cell fate choice be likely to be determined stochastically?
5.3 What types of behavior would be considered "cheating" in a transient metazoan?

Thursday, 14 September

6.Clonal metazoans & their evolutionary origins

→ slides after class zoom video

for the curious: The transition to multicellular life may not have been so hard after all

review beSocratic 5

Portfolio questions:
6.1 What factors may have driven the evolution of clonal multicellular organisms (animals)?
6.2 Why might you want to distinguish the soma and the germ line?
6.3 What types of behavior would be considered "cheating" in a clonal metazoan?

WEEK 4 – Tuesday 19 September

7. Evolutionary relationships & model systems
→ slides

for the excessivly curious: Simakov et al 2022. Deeply conserved synteny & the evolution of metazoan chromosomes

review beSocratic 6

Portfolio questions:
7.1 What makes for a good model system and what limits their relevance to humans?
7.2 What does it mean that a trait is homologous rather than analogous?
7.3 How do evolutionary adaptations influence development processes, such as the speed and mechanisms behind early embryonic development?

Thursday 21 September

8. Being bilateral: A-P axis & HOX clusters → slides

for the curious (on planaria): Arnold et al 2021. Hox genes regulate asexual reproductive behavior and tissue segmentation in adult animals

review beSocratic 7

Portfolio questions:
8.1 How do reproducible developmental phenotypes facilitate "forward" genetic studies?
8.2 How does the stereotyped embryonic lineage in C. elegans make possible studies of cell death during development?
8.3 How is a homeobox-containing gene different from a Hox gene?

WEEK 5 – Tuesday, 26 September

9. Finish axes/HOX - Learning from (clawed) frogs

→ slides

For the curious: Harrison 2020. The difference between "homeobox" and HOX genes.

review beSocratic 8

9.1 How did John Gurdon’s experiment help establish that genomic diminution in somatic cells was not happening in Xenopus?
9.2 What factors might contribute to making it more difficult to reprogram a somatic nucleus? 
9.3 Sketch out the stages of the reorientation of the Xenopus egg upon fertilization.

Thursday, 28 September

10. Learning from frogs →slides

review beSocratic 9

10.1 Describe the events during oogenesis and early development “set up” the embryonic axes.
10.2. What types of evidence lead one to conclude that mRNA (and protein) stability determined by their environment.
10.3 What types of evidence suggest that the Spemann-Mangold organizer is induced by more vegetal regions of the early Xenopus embryo?

WEEK 6 – Tuesday, 3 October

11. review Xenopus - Learning from the Zebrafish
→ slides

review beSocratic 10

Portfolio questions:
11.1 How did early embryonic asymmetries aid in identifying (natural) inductive molecules in Xenopus?
11.2 What makes zebrafish a good system for studying cellular aspects of development?
11.3 Where are inductive interactions occurring the early zebrafish embryo?

Thursday, 5 October

12. complete Zebrafish + consider single cells analyses
→ slides

Week 7 – Tuesday, 10 October

13. Exam 1 review exam practice

→ reviewslides

review beSocratic 12

Update your portfolios
– anything confusing,
let's talk about it.

2022 EXAM 1 review questions 

REVIEW QUESTION NOTES

Thursday,  12 October –– EXAM - on beSocratic (opens at 9AM - closes at midnight on Friday)

Exam 1 Answer  key– Fall 2023

Week 8 – Tuesday, 17 October

15. Learnin' from the worm and reproducible lineages
→ slides

background for the curious: Geraldine Seydoux: From Egg to Worm: How to Create a Body Axis

on nota bene and down-loadable here: Predicting mutation outcomes frm early stochastic variation in genetic interaction partners

Thursday 19 October  (midterm exam feedback)

16. Finishing the worm:: discovering the roles of non-coding RNAs in the worm   → slides

review beSocratic 15

Portfolio questions:
16.1 How did the nature of C. elegans development facilitate the discovery of miRNAs?
16.2 Describe the types of mutations in the lin4/lin14 system that produce similar phenotypes?

Week 9 – Tuesday 24 October

17. Learnin' from fruit fly - stereotyped phenotypes
→ slides

review beSocratic 16

Portfolio questions:
17.1 How do the features of Drosophila embryogenesis facilitate a forward genetic approaches to identifying the processes involved.
17.2 How might the early syncytial stage of Drosophila development favor maternal mRNA localization and translation (compare to C. elegans)

Thursday, 26 October

18. Drosophila continues→ slides

review beSocratic 17

Portfolio questions:
18.1 How do interactions between maternally encoded proteins influennce axis formation (both a-p and d-v)?
18.2 Which function is likely to be ancestral (for the NFkB system): innate immunity or axis specification in embryos?
18.3 While is likelly to have a more direct impact on HOX expression, segment polarity or a-p axis specification systems?

Week 10 – Tuesday, 31 October

19. Drosophila Dorsal-Ventral, segments & HOX
→ slides

background for the curious: Nipam Patel: The role of homeotic genes in development

review beSocratic 18

Portfolio questions:
19.1 What is the role of signaling and feedback in the context of establishing dorsal-ventral patterning (in the fly)?
19.2 How is "posterior prevelence" different between the fly and vertebrates?  (will will review this in class on the 2nd).

Thursday, 2 November

20. Early development in the mouse & human → slides

background for the curious: Cell competition and the regulatory nature of early mammalian development

Week 11 – Tuesday, 7 November

21. Early mammalian development continues → slides

background for the curious (good video): Labs growing human embryos for longer than ever before

Thursday, 9 November

22. Primitive streak and crest → slides

background for the curious: Human neural tube morphogenesis in vitro by geometric constraints

review beSocratic 21

Portfolio questions:
22.1 How is the patterning of the head region different from that of the trunck (somitic mesoderm)
22.2 What factors influence where a neural crest cell goes and what it differentiates into?
22.3 What defects in cellular behavior could lead to the failure of the neural tube to close

Week 12 – Tuesday, 14 November

23. neural crest & somite formation → slides

background for the curious: Mouse embryonic stem cells self-organize int trunk-like structures with neural tube and somites

review beSocratic 22

Portfolio questions:
23.1 How might you design a molecular clock to drive somite formation?
23.2 Why does a molecular clock (like the Hes7 loop) need to be reset periodically?
23.2 How do HOX genes influence somite differentiation?

Thursday, 16 November

24.Patterning & connecting the nervous system → slides

Newest stuff: Imaging the onset of oscillatory signaling dynamics during mouse gastrulation video worth watching: Holt: Wiring the brain – how axons navigate

Optional: videos Development of Spinal Nerves
somite (mouse) formation: video 4 & video 11

Portfolio questions:
24.1 How is the system that leads to different neural types (from ventral to dorsal), in the neural tube similar to the activin-Gsc-Xbra system described by Saka and Smith?
24.2 What is the distinction between attractive and repulsive signals in axon growth?
24.3 How could a neuron recognize it target?

20-24 Nov '2022 Fall Break & Thanksgiving

Fall Break & Thanksgiving

Week 13 – Tuesday, 28 November

25. Limb formation → slides

for the curious: Neil Schubin: The Origin of Four-Legged Animals & :The Evolution of Limbs from Fins

review beSocratic 23

Portfolio questions:
25.1 What determines where a limb will form along the body axis?
25.2 How different axes (e.g., A-P axis, D-V axis) are set up in the limb?
25.3 What is the role of regulated apoptosis in limb / autopod formation?

Thursday, 30 November

26.Limb development completed → slides

review beSocratic 24

Portfolio questions:
26.1 How does the Cre-Lox system work? how can it be turned on in a cell and timing specific manner?
26.2 How might you determine whether expression of Gli3 influences apoptosis?

Week 14 – Tuesday 5 December

27. Making and using induced pluripotent stem cells (iPSCs)  → slides

for the excessivly curious: Etoc et al., 2016. A Balance between Secreted Inhibitors and Edge Sensing Controls Gastruloid Self-Organization.

review beSocratic 25

Portfolio questions:
27.1 How do stem cells, embryonic, and induced pluripotent stem cells differ?
27.2 Why might the original iPSC protocol not work on all somatic cell types?
27.3 How might you introduce axes within an organoid?

Thursday 7 December

28. Organoids and synthetic embryos → slides (coming)

for the excessivly curious: Pinson et al., 2022. Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals. Science

review beSocratic 26

Portfolio questions:
28.1 How might you identify human specific genetic factors + then study their roles in the development of brains, behavior, and such? 
28.2 What are the ethical limits (if any) of using iPSC-derived organoids for understanding and treatment of human disease?
28.3 In the light of using organoids to study the effects of neanderthal genes in neural development, how might you use organoids to build a "better humans"? what outcomes would you worry about?

Week 15 – Tuesday 12 December

29. Genetic engineering: practical & ethical considerations
→ slides

for the excessivly curious: issues raised by synthetic human entities with embryo-like features + Polygenic Screening: What is the Use?

review beSocratic 27

Portfolio questions:
29.1  Should we recreate Neanderthals (or other "pre-humans")?
29.2 Should engineering for purposes other than avoding genetic diseases be allowed?

Thursday 14 December

30. Exam review  → slides

Final Exam Review

FINAL EXAM DAY and Time (set by University)
↓
EXAM 2 + GRADING NOTES 2022

Review & submit your portfolios by midnight
- bring confusions & clarifying questions to class