DDevelopmental Biology
MCDB 4650

DEVO@CU in 2021 is designed to introduce you to the key ideas, observations, experimental systems, and analytical methods used to study developing systems

face development

the syllabus may change now and then during the semester.  supplemental readings

Date / Topic                            

 

WEEK 1
1. Thursday, 14 Jan 2021
Professors Brumbaugh
+ Klymkowsky

What is the course about, how does it works & what you can expect?

slides + video
posted on canvas as well

 

If at all possible before class read: On teaching developmental biology in the 21st centrury
+ watch Sabine Hossenfelder's "Heisenberg's microscope
+ Richard Feynmann "explaining magnetic attraction"
+ think about how you learn


Questions & topics we will consider:
How does the course work?
What, exactly, is developmental biology?
What is important to learn and why, and how do we propose to help you learn it?
+ Building plausible explanatory mechanistic models + using beSocratic


 

2. Tuesday, 19 Jan
Klymkowsky

Genes, their regulation & threshold responses.

slides + video
posted on canvas as well

 

emo 1 complete post-class 1 beSocratic activity: introduction & making models
+
Read before class
: On teaching developmental biology in the 21st centrury
+ Thinking about biological thinking: Steady state, half-life & response dynamics


Questions & topics we will consider:
What factors influence the genes expressed in a cell?
How do cells respond to signals? How do threshold responses work?
When and why is gene expression noisy?
How do cell exploit and control stochastic processes?
How do cells with the same genotype develop different phenotypes?
How is that that phenotype is stable?


Dossier question
Why are dose-response curves typically sigmoidal?
Describe a simple model that produces a threshold response.
What features of a response can make a dose response stable or unstable over time?
How can cells with the same genotype produce different phenotypes?


 

WEEK 2:
3. Thursday,  21 Jan.
Klymkowsky

Quorum sensing & aggregative multicellularity

slides + video
posted on canvas as well

 

emo 1complete post-class 2 beSocratic activity: Gene expression & noise
Read: Aggregative and clonal metazoans


Questions & topics we will consider:
What are the advantages of cooperation / transient multicellularity?
How do microbes sense the world (and each other)?
Why is there quorum sensing?


Dossier questions
all of the above +
How could a slime mold cell cheat and why must cheating be kept under control?


 

4. Tuesday, 26 Jan
Klymkowsky

Clonal multicellularity:
germ line & the soma

slides + video
posted on canvas as well
code: .6$LPnt3



 

emo 1 complete post-class 3 beSocratic activity: Quorum sensing


Questions & topics we will consider:
What are the advantages of clonal multicellularity? 
What factors lead to different cell types?
How are differentiated cells recognized?


Dossier questions
all of the above



 

WEEK 3:
5. Thursday, 28 Jan
Klymkowsky

Asymmetries & cellular differentiation

slides + video
posted on canvas as well
code: QJv5d#BN

 

emo 1complete post-class 4 beSocratic activity: Soma & germ line
Watch : single cell RNA seq + ATAC-Seq: Mapping Open Chromatin videos 


Questions & topics we will consider:
Why is there a somatic/germ layer divide?
How are asymmetries established or arise?
How do they influence gene expression?


Dossier questions
How does cell differentiation become (effectively) irreversible?
Why might the original iPSC protocol not work on all somatic cell types?


 

6.Tuesday, 2 February
Klymkowsky

Continue asymmetries & left-right axes

slides + video
Passcode: v#f6ayU+ 
posted on canvas as well

 

emo 1complete post-class 5 beSocratic activity:  Cellular differentiation


Questions & topics we will consider:
How do molecular asymmetriesand embryonic handedness arise; how do they influence gene expression and cellular differentiation?


Dossier questions
What are the cellular originsl of embryonic left-right asymmetries?


 

WEEK 4:
7. Thursday, 4 Feb.
Klymkowsky

Complete left-right & signaling systems

slides + video
Passcode: m8fJU*1P
posted on canvas as well

 

emo 1complete post-class 6 beSocratic activity: Cellular asymmetries


Questions & topics we will consider:
Interactions between cellular (myo1D), ciliary & nodal l-R asymmetry mechanisms.
How are asymmetry decisions reinforced?
What makes the outcomes of signaling systems difficult to predict?

elephant's child
optional reading for the excessively curious only Animal left-right asymmetry


Dossier questions
What makes chimeric protein possible and useful?



 

8. Tuesday, 9 Feb
Klymkowsky

Model systems: uses & limitations

slides + video
Passcode: 6geswjw$ 
+ posted on canvas

 

emo 1complete post-class 7 beSocratic activity: LR polarity effects


Questions & topics we will consider:
What makes for a good model system?
What are the limits of various model systems?
What exactly are we trying to model?


Dossier questions
What are the limits of various model systems?
How can evolutionary adaptions influence development processes?


 

Weeek 5:
9. Thursday, 11 Feb
Klymkowsky

Model Systems completed +
Establishing (AP) axes and Hox genes

slides + video
Passcode: O41#DR8* 
posted on canvas

 

emo 1complete post-class 8 beSocratic activity: model systems


Questions & topics we will consider:
How (generally) are embryonic (A–P) asymmetries established?
How (antagonistic) signaling systems pattern embryos
And what is so cool about the HOX cluster?


Dossier questions
How are homeobox-containing genes different from the Hox cluster genes?



 

10. Tuesday, 16 Feb
Klymkowsky

Finish Hox +
Learning from
frogs begins

slides + video
Passcode: +h$SS8Mm 
posted on canvas

 

emo 1complete post-class 9 beSocratic activity
Optional review: Richard Harland Xenopus: parts 1 and 2 through [link] to ~12:30
Xenopus: Time-lapse through neurulation


Questions & topics we will consider:
What makes xenopus a good system for studying cellular aspects of development?
What are its limitations?
How does sperm entry interact with oocyte asymetries to generate embryonic axes?
How are changes in cell shape coordinated to produce epiboly & convergent extension?

Dossier questions
How does gravity influence Xenopus development?


 

11. Week 6
Thursday, 18 Feb

Klymkowsky

Learning from
fish completed

slides + video
Passcode: *cR5Lj=F
posted on canvas

 

emo 1complete post-class 9 beSocratic activity: Xenopus


Questions & topics we will consider:
What makes zebrafish a good system for studying cellular aspects of development?
How is sperm entry constrained?
How has zebrafish been used to examine axis formation?


Dossier questions
How does noise in Wnt signaling arise, and
how is it suppressed (in zebrafish and likely elsewhere)?



 

12. Tuesday, 23 Feb

Single cell RNA seq
studies of differentiation

slides + video
Passcode: GB!@8Ms^ 

+ video posted on canvas

 

emo 1complete post-class 10/11 beSocratic activity: xenopus & zebrafish
read:  Biology education in the light of single cell/molecule studies
Watch: StatQuest: Principal Component Analysis (PCA) (20 min.)
please excuse the ads

(very optional reading: principle component analysis explained simply)


Questions & topics we will consider:
What does a principle component tell us?
Why don't cells of the "same type" display exactly the same patterns of gene expression?


Dossier questions
How would a scRNA-SEQ analysis reveal the effects of allelic differences?



 

WEEK 7
13. Thursday, 25 Feb

Klymkowsky

Learning from worms (as a model system)

slides + video
Passcode: N%42a!5*
+ video posted on canvas

 

emo 1complete post-class 12 beSocratic activity: single cell studies


Questions & topics we will consider:
How do the details of C. elegans development facilitate studies of development mechanisms?
• specifically consider the case of apoptosis


Dossier questions
Predict how (and why) explants of C. elegans embryos would differ from those of Xenopus and zebrafish ?


 


Tuesday., 2 March

14. Klymkowsky

2020 midterm 1

video
Passcode: 0BXMs4*8
+ video posted on canvas


 

emo 1complete post-class 13 beSocratic activity: worms

update your dossiers and bring questions to class

2020 review questions 


 

WEEK 8:
15.Thursday, 4 March
Klymkowsky

Exam one

 

First EXAM Spring 2021

 EXAM #1  First exam 2021 answer key 

 

16. Tuesday, 9 March
Brumbaugh

Mutations, screens & geneediting

slides
+ video  
Passcode: 9%SY7D*b
posted on canvas

 

Questions & topics we will consider:
What is the difference between exploratory (forward) and manipulative (reverse) genetics?
How do you interpret a loss of function mutation and a gain of function mutation?


Dossier questions
Give one example of exploratory (forward) and manipulative (reverse) genetics in the context of developmental biology.
Why is each approach powerful?
What is the difference between a loss of function mutation and a gain for function mutation?
How can each be useful in the context of molecular biology?


 

WEEK 9:
17.Thrusday, 11 March
Brumbaugh

Signaling

slides
+ video
Passcode: &2iwe&kn
posted on canvas

 

emo 1complete post-class 16 beSocratic activity: mutations


Questions & topics we will consider:
What cellular components are involved in signaling and how are these engaged?
What is a morphogen and why is it important for development?


Dossier questions
Why do cells need to communicate with each other during development?
How do cells signal between one another or to themselves?
Why are there different signaling modes?



 

18. Tuesday, 16 March
Brumbaugh

Early Drosophila axes

slides
+ video
Passcode: Lmn0m@+.  posted on canvas

 

emo 1complete post-class 17 beSocratic activity: signaling


Questions & topics we will consider:
How do maternal effect genes influence early embryogenesis?
How are genes organized to generate a hierachy in developmental regulation?


Dossier questions
Why is it necessary to have certain transcripts already deposited in the egg by the mother (i.e., maternal effect genes)?
Why is having a syncitium contribute to developmental mechanisms in Drosophila?
Why have competing gradients of transcriptional activators and translational repressors (think about Hunchback)?



 

WEEK 10:
19. Thursday, 18 March
Brumbaugh

Drosophila embryonic larval patterning

slides + video
Passcode: 2?r!&?wm
posted on canvas

 
emo 1complete post-class 18 beSocratic activity: Drosophila axes

Questions & topics we will consider:
How did homeotic transformations help developmental scientists in identifying gene responsible for specifying identity?


Dossier questions
How would you test whether a particular region acts as an enhancer for a developmental gene? 
Why is signaling important for setting up segmentation?


 

20. Tuesday, 23 March
Brumbaugh

Hox genes & segmentation in Drosophila

slides + video
Passcode: %eCG.0TL
posted on canvas

 
emo 1complete post-class 19 beSocratic activity: larval patterning

Questions & topics we will consider:
How did homeotic transformations help developmental scientists in identifying gene responsible for specifying identity?


Dossier question
What happens if you inappropriately express a hox gene in a segment where it is not normally found?
What regulates the posterior-most boundary of hox gene expression?
How do histone modifications contribute to segment identity?


 

WEEK 11:
Thursday, 25 March

 

campus wellness day and nothing due! take care of yourself (and others)


 

22. Tuesday, 30 March
Brumbaugh

Stem cells and embryonic cleavage

slides + video 
Passcode: !7Te62sH

posted on canvas

 

emo 1complete post-class 20 beSocratic activity: Hox & segmentation


Questions & topics we will consider:
What defines a stem cell? What are induced pluripotent stem cells and how are they derived? How does cleavage plane orientation influence development?


Dossier questions
How is a totipotent cell different from a pluripotent cell?
How is a pluripotent cell different from a multipotent cell?
Why are induced pluripotent stem cells so important from both a practical and ethical point of view?


 

WEEK 12:
23. Thursday, 1 April
Brumbaugh

Gastrulation & neurulation

slides + video
+  Passcode: 1$4Q1dyg

posted on canvas

 

emo 1complete post-class 22 beSocratic activity: stem cells
Mouse : Animation: Second Week Of  Development
Animation: Gastrulataion | Neurulation


Questions & topics we will consider:
How do early signaling pathways and cell movements specify cell identity?
What mechanisms are used to specify cell fate in both gastrulation and neurulation?


Dossier questions
What determines the fate of ectoderm in neurulation? 
How does cell division influence the first lineage decision in the blastocyst?


 

24. Tuesday, 6 April
Brumbaugh

Axon guidance & target selection

slides
+ video
Passcode: 3M+qG0PN

posted on canvas

 

emo 1complete post-class 23 beSocratic activity: gastrulation and neurulation


Questions & topics we will consider:
How do neurons find their targets and what happens if this process is disrutped?
What tools have scientists used to tease apart the mechanisms that control neural connectivity?


Dossier questions
Axon guidance is determined by both positive and negative cues.
Explain how each cue works to direct axons.
How can you design an experiment to determine whether an axon guidance cue is attractive or repulsive?


 

WEEK 13:
25. Thursday, 8 April
Brumbaugh

Neural crest

slides + video
Passcode: ai*.M88?

posted on canvas

 

emo 1complete post-class 24 beSocratic activity: axon guidence


Questions & topics we will consider:
What cell types are born of neural crest cells?
How are these cell specified?


Dossier questions
How do you induce epidermal cells to adopt three different fates (neural ectoderm, neural crest, non-neural ectoderm?
Why is the migration path of neural crest cells so important?



 

26. Tuesday, 13 April
Brumbaugh

Mammalian segmentation & somite formation

slides
+ video
Passcode: X2$.=Fyh + posted on canvas

 

emo 1complete post-class 25 beSocratic activity: neural crest


Questions & topics we will consider:
What similarities do we see between mammalian and Drosophila segmentation?
How do somites arise?


Dossier questions
What signals do you need to specify a somite?
What happens to somite formation if you disrupt these signals?



 

WEEK 14:
27. Thursday, 15 April
Klymkowsky

Studing developmental processes and defects in humans

slides
+ video
Passcode: Y*HS341S 

posted on canvas

 

emo 1complete post-class 26 beSocratic activity: Mammalian segmentation


Questions & topics we will consider:
What limits the use of animal models in studies of human disease?
How do we identify human specific genetic factors +
then study their roles in development of brains, behavior, and such? 
How do we distinguishing genetic from environmental effects?


Dossier questions:
How might you introduce axes within an organoid?
What are the ethical limits (if any) of use of iPSC-derived organoids for understanding and treatment of human disease?
In the light of using organoids to study the effects of neanderthal genes in neural development, how could you use organoids to build a "better humans"; what outcomes would you worry about?

Optional reading:
Human organoids: model systemsfor human biology and medicine
Reintroduction of the archaic variant of NOVA1 incortical organoids alters neurodevelopment


 

28. Tuesday, 20 April
Brumbaugh

Limb formation

slides
+ video
Passcode: 9mu@EuHNposted on canvas

 

emo 1complete post-class 27 beSocratic activity: Developmental defects
watch : The Evolution of Limbs from Fins - Neil Shubin  2016


Questions & topics we will consider:
How different axes (e.g., A-P axis, D-V axis) are set up in the limb?
Which signaling modes are established to determine patterning in the limb?


Dossier questions
What determines where a limb will form along the body axis?
Why is apoptosis crucial for limb formation?



 

WEEK 15:
29. Thursday, 22 April
Brumbaugh

Mouse transgenics

slides
+ video
Passcode: bHh6=f^p
posted on canvas

 

emo 1complete post-class 28 beSocratic activity: limb formation

watch and read: Gene editing is here. It’s an enormous threat.


Questions & topics we will consider:
Understand the components that go into targeting constructs for genome editing.
How do we make mouse models?


Dossier questions
Why are transgenics so powerful for studying developmental biology?
Describe how conditional knockouts are achieved?


 

30. Tuesday, 27 April
Brumbaugh + Klymkowsky

Catch-up & Course review

slides + video
Passcode: 6fmR9l%$

posted on canvas

 

emo 1complete post-class 29 beSocratic activity: mouse transgenics

review questions
+ 2019 exam answer key (different from this year's)

     

31. Thurs, 29 April

Course review
(2:20 to 3PM)

 

REVIEW SESSION + HOX REVIEW slides

SECOND EXAM opens at 3PM closes at 10PM


 

 

 
Dossiers due 4th May 2021 @ 7PM


  cell and molecular and developmental
education


The original version of DEVO@CU
by M.W. Klymkowsky/virtuallaboratory/beSocratic, llc.
Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License
.  2019-2020