M3 L20: Developmental genetics Flashcards
what is development
process by which a single celled zygote differentiates into a multicellular organism
what did johann wolfgang von goethe contribute to our understanding of development
best way to study it is to study abnormalities
what did ernst haeckel contribute to our understanding of development
discovered all animal species develop similarly –> support for evolution from a common ancestor like Darwin proposed
what was calvin bridges’ contribution to our understanding of development
discovered the first developmental mutant - the bithorax mutant that causes hind wings in drosophila
what are homeotic mutations and examples? what do they help us understand
mutations that cause body parts to develop in abnormal areas
help us understand how dif patterns of development are established
bithorax mutation
antennapedia mutation
what cells are totipotent
ones that can develop into any tissue type
zygotic cells and embryonic stem cells
what is differentiation
changes in gene expression that result in different physiological activities (all somatic cells are still genetically identical)
what is waddington’s epigenetic landscape
idea that as differentiation progresses, it limits what genes can be expressed/what fate the cell can acquire
what are pluripotent cells
cells that can develop into many but not all types of cells
what is pattern formation
process by which embryo establishes the 3 main body axes
dorsal/ventral
L/R
anterior/posterior
how do genetically identical cells know where they are, what they’re supposed to do, and acquire different fates?
receive positional info from morphogens which exist in concentration gradients –> gradients + thresholds = discrete boundaries of gene expression (what genes are on vs off)
how can cells affect neighboring cells
after a cell’s fate is determined, they can induce or inhibit neighboring cells via receptors, signaling molecules, TFs
what is asymmetric cell division
daughters have different transcription factors/chromatin states/cell components than parent cell (very rare)
what is developmental history of a cell and why does it matter
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
what’s a syncytium
multinucleate cell where the nuclei aren’t separated by cell membranes (early in drosophila development after 9 rapid cell division cycles)
what are pole cells
~10 cells that move to the periphery at the posterior end of the embryo –> give rise to the germ line
what is the syncytial blastoderm
structure in drosophila development after the somatic nuclei undergo 4 more divisions
what is the cellular blastoderm
structure in drosophila development after cellularization of syncytial blastoderm
what are housekeeping genes? at what stage in development would you need to study them?
needed in all cells and direct patterns of development
need to study in larvae/embryos bc abnormally developing embryos don’t reach adulthood
what are the 5 classes of developmental genes in drosophila and their functions
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
what are maternal effect genes? why do they have different inheritance patterns than zygotic genes?
proteins/mRNAs that the mother deposits in the embryo –> direct development
dif inheritance pattern bc they reflect the maternal genotype not the zygote genotype
when does the maternal to zygotic transition occur
syncytial blastoderm stage
how is initial spatial patterning directed?
gradient of maternally deposited bicoid mRNA (high concentration at anterior end)
how is hunchback expression determined?
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
example of a pair rule gene? how is it regulated
even skipped
regulated by complex enhancer elements each with many TF binding sites
how is even skipped only expressed in parasegment 3
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
what are segment polarity gene examples
wingless and engrailed (wingless at anterior, engrailed at posterior)
how does runt in drosophila relate to humans
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
how are hox genes typically present in genomes
single clusters
evidence hox genes cane from duplication and neofunctionalization
all hox genes are part of a gene family, meaning there are other genes with similar functions (which likely came from duplication and neofunctionalization)
are hox genes necessary for defining segments? identifying segments? how do we know?
segment will still develop as head by default if no hox genes –> not necessary for defining segments but necessary for segment identity
how do hox genes support ohno’s idea of gene duplication and evo innovation
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)
how do we know regulatory mutations are viable? why are they more viable than LOF muts?
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
what happens if you mutate hox10 in mice? what is this an example of?
mutate hox10 –> lumbar vertebrae develop as ribs
reverse genetics (start with sequence and identify phen change)
what’s the purpose of the anchor cell in c. elegans
secrete inductive signal to drive a precursor cell to develop into a primary cell for the vulva
how do precursor cells determine which one becomes the primary cell?
whichever has the threshold amount of inductive signal
what LOF mutations lead to c. elegans without vulvas
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)
GOF muts in which genes lead to multivulva c. elegans
let-23 and let-60
how to infer order of genes in pathway (the 3 genes where LOF causes no vulva)
phenotype reflects whichever mutation (GOF or LOF) is latest in the pathway
what is lateral inhibition
reinforce asymmetry in a signal by communicating with other cells nearby
roles of lag-2 and lin-12 in lateral inhibition
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
purpose of apical ectodermal ridge
direct growth of limb bud
purpose of zone of polarizing activity
secrete shh and direct AER to direct limb bud dev
impact of too much shh
polydactyly
why do extra digits always have same identity as adjacent digit?
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)
