M3 L20: Developmental genetics

Question 1

what is development

Answer 1

process by which a single celled zygote differentiates into a multicellular organism

Question 2

what did johann wolfgang von goethe contribute to our understanding of development

Answer 2

best way to study it is to study abnormalities

Question 3

what did ernst haeckel contribute to our understanding of development

Answer 3

discovered all animal species develop similarly –> support for evolution from a common ancestor like Darwin proposed

Question 4

what was calvin bridges’ contribution to our understanding of development

Answer 4

discovered the first developmental mutant - the bithorax mutant that causes hind wings in drosophila

Question 5

what are homeotic mutations and examples? what do they help us understand

Answer 5

mutations that cause body parts to develop in abnormal areas

help us understand how dif patterns of development are established

bithorax mutation

antennapedia mutation

Question 6

what cells are totipotent

Answer 6

ones that can develop into any tissue type

zygotic cells and embryonic stem cells

Question 7

what is differentiation

Answer 7

changes in gene expression that result in different physiological activities (all somatic cells are still genetically identical)

Question 8

what is waddington’s epigenetic landscape

Answer 8

idea that as differentiation progresses, it limits what genes can be expressed/what fate the cell can acquire

Question 9

what are pluripotent cells

Answer 9

cells that can develop into many but not all types of cells

Question 10

what is pattern formation

Answer 10

process by which embryo establishes the 3 main body axes

dorsal/ventral
L/R
anterior/posterior

Question 11

how do genetically identical cells know where they are, what they’re supposed to do, and acquire different fates?

Answer 11

receive positional info from morphogens which exist in concentration gradients –> gradients + thresholds = discrete boundaries of gene expression (what genes are on vs off)

Question 12

how can cells affect neighboring cells

Answer 12

after a cell’s fate is determined, they can induce or inhibit neighboring cells via receptors, signaling molecules, TFs

Question 13

what is asymmetric cell division

Answer 13

daughters have different transcription factors/chromatin states/cell components than parent cell (very rare)

Question 14

what is developmental history of a cell and why does it matter

Answer 14

anything that’s happened to the cell in development up to that point

1) expression of lack of expression of certain receptors affects sensitivity to signaling molecules

2) different cells might respond differently to the same signal depending on other factors within each cell

Question 15

what’s a syncytium

Answer 15

multinucleate cell where the nuclei aren’t separated by cell membranes (early in drosophila development after 9 rapid cell division cycles)

Question 16

what are pole cells

Answer 16

~10 cells that move to the periphery at the posterior end of the embryo –> give rise to the germ line

Question 17

what is the syncytial blastoderm

Answer 17

structure in drosophila development after the somatic nuclei undergo 4 more divisions

Question 18

what is the cellular blastoderm

Answer 18

structure in drosophila development after cellularization of syncytial blastoderm

Question 19

what are housekeeping genes? at what stage in development would you need to study them?

Answer 19

needed in all cells and direct patterns of development

need to study in larvae/embryos bc abnormally developing embryos don’t reach adulthood

Question 20

what are the 5 classes of developmental genes in drosophila and their functions

Answer 20

1) coordinate genes: establish initial anterior and posterior

2) gap genes: divide embryo into broad regions

3) pair rule genes: define segment borders

4) segment polarity genes: establish anterior/posterior axis in each segment

5) hox genes: define segment identity

Question 21

what are maternal effect genes? why do they have different inheritance patterns than zygotic genes?

Answer 21

proteins/mRNAs that the mother deposits in the embryo –> direct development

dif inheritance pattern bc they reflect the maternal genotype not the zygote genotype

Question 22

when does the maternal to zygotic transition occur

Answer 22

syncytial blastoderm stage

Question 23

how is initial spatial patterning directed?

Answer 23

gradient of maternally deposited bicoid mRNA (high concentration at anterior end)

Question 24

how is hunchback expression determined?

Answer 24

mother deposits bicoid at anterior region (activates hunchback expression), nanos at posterior region (inhibits hunchback expression) –> dif concentrations give positional info and drive dif patterns of expression

Question 25

example of a pair rule gene? how is it regulated

Answer 25

even skipped regulated by complex enhancer elements each with many TF binding sites

Question 26

how is even skipped only expressed in parasegment 3

Answer 26

the even skipped enhancer has binding sites for bicoid, hunchback, (activating) kruppel, and giant (deactivating) bicoid and giant are both present in parasegments 1-2 so giant silences even skipper kruppel and hunchback are both in parasegments 4-6 so kruppel silences even skipped no even skipped silencers are present in parasegment 3 --> even skipped expressed in that segment

Question 27

what are segment polarity gene examples

Answer 27

wingless and engrailed (wingless at anterior, engrailed at posterior)

Question 28

how does runt in drosophila relate to humans

Answer 28

runt aids in sex determination and nervous sys dev in drosophila mutations in human homolog lead to cleidocranial dysplasia (hole in top of skull and no collar bones) homo mut in mouse homolog prevent bone ossification and are lethal a drosophila TF helped us identify genes that are important for human development

Question 29

how are hox genes typically present in genomes

Answer 29

single clusters

Question 30

evidence hox genes cane from duplication and neofunctionalization

Answer 30

all hox genes are part of a gene family, meaning there are other genes with similar functions (which likely came from duplication and neofunctionalization)

Question 31

are hox genes necessary for defining segments? identifying segments? how do we know?

Answer 31

segment will still develop as head by default if no hox genes --> not necessary for defining segments but necessary for segment identity

Question 32

how do hox genes support ohno's idea of gene duplication and evo innovation

Answer 32

hox genes are animal specific and vertebrates have 4 clusters (likely from duplications --> hox genes now free to vary bc many copies --> allow for major transitions like dev of vertebrae)

Question 33

how do we know regulatory mutations are viable? why are they more viable than LOF muts?

Answer 33

mut in regulatory seqs for antennapedia and ultrabithorax are viable but LOF mut in the genes are not more viable for 2 reasons 1) some functional protein still being made 2) modularity: changing the regulatory sequence doesn't completely change the protein sequence/proper expression

Question 34

what happens if you mutate hox10 in mice? what is this an example of?

Answer 34

mutate hox10 --> lumbar vertebrae develop as ribs reverse genetics (start with sequence and identify phen change)

Question 35

what's the purpose of the anchor cell in c. elegans

Answer 35

secrete inductive signal to drive a precursor cell to develop into a primary cell for the vulva

Question 36

how do precursor cells determine which one becomes the primary cell?

Answer 36

whichever has the threshold amount of inductive signal

Question 37

what LOF mutations lead to c. elegans without vulvas

Answer 37

lin-3: the inductive signal (anchor cell can't secrete it) let-23: the receptor (precursor cels can't receive inductive signal) let-60: signal transduction molecule (can't tell nucleus that let-23 is bound and to change pattern of expression to dev into primary cell)

Question 38

GOF muts in which genes lead to multivulva c. elegans

Answer 38

let-23 and let-60

Question 39

how to infer order of genes in pathway (the 3 genes where LOF causes no vulva)

Answer 39

phenotype reflects whichever mutation (GOF or LOF) is latest in the pathway

Question 40

what is lateral inhibition

Answer 40

reinforce asymmetry in a signal by communicating with other cells nearby

Question 41

roles of lag-2 and lin-12 in lateral inhibition

Answer 41

if lin-3 binds lag-2, the cell upregulates lin-12 and downregulates produciton of lag-2 (more responsive to external lag-2) --> does not develop as primary cell if lin-3 does not bind lag-2, the cell upregulates lag-2 and downregulates lin-12 (less responsive to external lag-2) --> does develop as primary cell

Question 42

purpose of apical ectodermal ridge

Answer 42

direct growth of limb bud

Question 43

purpose of zone of polarizing activity

Answer 43

secrete shh and direct AER to direct limb bud dev

Question 44

impact of too much shh

Answer 44

polydactyly

Question 45

why do extra digits always have same identity as adjacent digit?

Answer 45

extra digit must express whatever hox genes are in that area (will be the same as the ones expressed by the digits next to it)