Flashcards
developmental biology - genetics
Cards in this deck (20)
- 1development involved cell division - cleavage divisions can set up asymmetries by segregating determinants polarised parental cell -> asymmetric localisation of cell-fate determinants -> unequal daughter cellsas cell divides, cells get smaller (no over growth)
- starting cell is polarised (molecular component unequally localised within cell), anchors to cytoskeleton & only apparent in half of cell
- when divides, division sets up difference between two daughter cells
- both now have different developmental pathways - 2pattern formation = process by which spatial & temporal pattern of cellular activities is organised with embryo so well-ordered structure develops - allocation to different germ layers: endoderm(gut), mesoderm(muscle), ectoderm(skin & NS) - cell is allocated to one germ layerregional specification = cells must know where they are & differentiate accordingly
- positional info in form of inherited cytoplasmic determinant, short or long-range signals
3 axis:
- anterior-posterior
- dorsal-ventral
left-right - 3morphogenesis = creation of structure & form - differential proliferation - change in individual cell shape & size - cell movement - cell fusion - cell deathgastrulation moves germ layers relative to one another
- whole-scale movement
- to begin with = all ectoderm concentrated at top & endoderm concentration at bottom, mesoderm as internal equator
- ectoderm spreads to cover while area of embryo, endoderm becomes internalised - 4little growth in early development, basic body plan is being established - differential growth rates result in change in body proportions - growth brought about by cell proliferation - cells become larger by taking on water/lipid & secretion of materials outside of cell - growth can be uniform or differentialzygote = totipotent
totipotent = gives rise to everything, all germ layers & extra-embryonic tissue
- all become specialised to tissues they form - 5early embryonic cells = pluripotent - potential gradually becomes restricted differentiation = process of becoming structural & functionally specialised, reflecting activation of gene expression pluripotent = able to give rise to all different tissues of body (germ layers) but no extra-embryonic membrane zygote -> blastula -> gastrula -> germ cells, ectoderm, endoderm & mesodermcleavage produces cluster of blastomeres
- division in absence of growth (cells get smaller) = blastomeres
- spherical blastomeres form loose clump
morula froms 3 days after fertilisation (undergoes compaction)
- increased cell-cell adhesion maximises contact between blastomeres, forming compact ball of cells held together by tight junction
- E-cadherin becomes restricted to regions of intracellular contact -> binds tight between cells, pulling cells together - 6outer cells have distinct apical & basal surfaces (apical have microvilli) - non-polarised cells form inner cell mass - inner cells communicate through gap junctions - 8-cell stage = cells all same - 16-cell stage = begin to differ due to cleavage plan radial cleavage = two daughter cells identical to each other tangential cleavage = two daughter cells different from one anothersegregation of trophectoderm & inner cell mass lineages is first differentiation event in mammalian embryonic development
- blastocyst embryo - two distinct areas:
-inner cell mass
- trophectoderm - 7blastocyst = embryo when fluid-filled cavity develops 1. inner cell mass will give rise to embryo proper (+some extra-embryonic structures) 2. zona pellucida prevents implantation in oviduct 3. flattened epithelial cells of trophectoderm will form extra-embryonic tissues 4. fluid-filled blastocyst cavityactive transport of Na ions = fluid accumulation in blastocoel
- tight junctions between outer cells act as permeability barrier
- Na+ actively transported into blastocoel
ion conc in blastocoel increases, water flows in by osmosis
- resulting hydrostatic pressure inflates blastocoel - 8enzymes digest through zona pellucida & embryo hatches - zona pellucida prevents embryo implanting into oviduct too early before has travelling into uterus - need to hatch to implant into uterus - enzymes digest & weaken zona pellucida, embryo pulses against weakened patch to emerge (5-6 DAF) trophoblast & inner cell mass splits into hypoblast & epiblastimplantation requires mutual interactions between trophoblast cells & uterine cells
- trophoblast cells express integral proteins
- these interact with extracellular matrix proteins expressed by epithelial cells of uterine mucosa (proteins = laminin &fibronectin
- integrin/laminin interactions promote attachment
- integrin/fibronectin interactions promote migration
inner cell mass = embryoblast - 9embryoblast - forms flat disc of two layers: epiblast & hypoblast epiblast: - columnar cells adjacent to newly formed amniotic cavity (forms embryo proper) hypoblast: - small cuboidal cells adjacent to blastocyst cavity - will form extra-embryonic structures that will connect to mothers circulationprimitive streak forms after two weeks
- primitive streak forms on surface of epiblast in region that becomes posterior of embryo (first sign of anteroposterior axis)
- during gastrulation epiblast cells migrate towards primitive streak & invaginate displacing hypoblast - 10during gastrulation - epiblast cells migrate through primitive streak to create 3 germ layers: - frist cells form endoderm - second cells form mesoderm - remaining epiblast cells form ectoderm morphology distinct & different for each later - flat embryo rapidly folds into three-dimensional bodyneurulation - ectoderm folds along central axis forming neural tube
- neural folds elevate & fuse
- neural crest cells form near site of fusion & migrate away
- epidermis fuses above neural tube - 11mesoderm segments into somites - somites generate trunk & limb muscles, dermis & vertebrate endoderm is internalised & gives rise to epithelial lining of GT - also provides stomach, liver & pancreasembryonic period (3-8W) - germ layers give rise to tissues & organogenesis
- stem cell populations establishing each organ primordia & sensitive to genetic & environmental influences
* period when most structural birth defects are induced - 12development stages of most animals: - fertilisation - cleavage to form blastula - gastrulation to reorganise structure of embryo & generate germ layers - neurulation - organogenesisepigenesis = progressive development - embryo with few cell types refined to generate complex organism with many cell types showing highly detailed organisation
- 13differentiated cells characterised by proteins they containgenomic equivalence = all somatic cells have complete copy of genome
- differentiated cell's nucleus can direct development of complete new individual, proving it doesn't lose genetic potential when becomes specialised - 14differential gene expression underlies differentiation -during cleavage, cells become different from one another - achieved by cytoplasmic determinants (transcription factors) - determinants specify body axes & influence gene expression, affecting cells developmental fate - interactions between cells influence their fate & bring about differentiation of specialised cell typesinductions are mediated by diffusible signals or by cell-surface interactions
asymmetric division = sister cells born different
symmetric division = sister cells become different as result of influences acting on them after birth
proteins that control orientation of mitotic spindle segregate with P-granules - 15model organism: suitable for experiments that address our question about embryo development e.g. mouse, fruit fly, frog (Xenopus)Xenopus eggs have visible & molecular polarity (animal hemisphere is pigmented)
- eggs are large
- Vg1 (localised in vegetal pole) encodes signalling molecule
- VegT encores transcription factor molecule - 16vegetally-localised VegT required for development of endoderm & mesoderm Veg-T binds DNA & actives expression of: - transcription factors that mediate endoderm differentiation - nodal TFGß factor that are secreted and induce responding cells to form mesodermmolecule must be:
- expressed in right cells at right time
- necessary for that function to take place
- sufficient for that function to take place
3 proof experiments:
1. VegT mRNA & protein can be detected in cells that will give rise to endoderm
2. removing VegT from oocyte interferes with both endoderm development & mesoderm induction
3. VegT expresson in ectoderm results in expression of endoderm-specific genes - 17Wnt signalling causes ß-catenin to accumulate in nucleus & active target gene expression: - absence of Wnt, GSK-3 active & destroys protein - GSK-3 inactive, ß-catenin enters nucleus & switch on expression of Wnt target genes, TCF converted from repressor to activator (gene expression turned on)sperm entry triggers cortical rotation
- translocating dorsal determinants that initiate Wnt signalling & establish dorsoventral axis
- after cortical rotation, dorsal determinants active Wnt signalling & inhibit GSK-3 on future dorsal side
- ß-catenin stabilised & enters nuclei on dorsal side (ventral nuclei don't receive ß-catenin)
*ß-catenin essential for dorsal development - 18ß-catenin activates expression of dorsal transcription factors such as goosecoid - interacts with Tcf-3 to activate expression of siamois (activates expression of goosecoid)VegT & ß-catenin activate nodal expression, resulting in high nodal gradient across endoderm - induces the organiser (low nodal induces ventral mesoderm)
- organiser secretes signals that pattern mesoderm & neutralise dorsal ectoderm
- grafting dorsal organiser cells to ventral side induces secondary axis - 19cell differentiate in response to received signals: - tells cells positional info & regional specification - cells respond by activating transcription factors that turn target genes on/off - combination of transcription factors determines which tissue-specific genes it expresses & how it differentiatessignals from surrounding tissues pattern mesodermal somites - differentiates into muscle
- signals induce expression of muscle-inducing transcription factors e.g. MyoD
- differentiate into skeletal muscle
- combination of transcription factors ensures cells express appropriate tissue-specific gene
MyoD can activate own expression (positive-feedback loop) - 20over expression of MyoD can convert non-muscle cells in muscle cell - single protein can act as master switch initiating complex programme of differentiation - important regulatory proteins carefully regulatedcell lineage = developmental history of differentiated cell, traced back to cell from which it arises
*transcription is fundamental level of control of differential gene expression during development
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- Flashcards on developmental biology - genetics , created by michaela minkin on 22/05/2018.
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