Exam III Flashcards
What are the 5 characteristics of cleavage?
- Multicellular
- Shape constant (mostly circular)
- Cytoplasm constant (not redistributed)
- Little growth (1>2>4)
- Nucleus to cytoplasm ratio increases
Do cleavage rates increase at a linear or exponential rate?
Exponential
How do rates of cleavage and rates of cancer cell division compare?
There are very similar; cancer cells come close to the rate of division seen during cleavage
How is the normal pathway that controls the cell cycle changed during cleavage?
The G1 and G2 phases are removed
Driven by MPF (active Cdc2 protein kinase)
Definition of karyokinesis
Separation of chromosomes
Definition of cytokineses
Separation of cytoplasms
What cell molecule dictates cell division?
Spindle
What was Rappaport’s experiment?
He put a glass bead in the middle of a dividing cell which displaces the spindle > furrow forms only on one side of cell, producing a binucleate egg > both nuclei enter mitosis > cleavage occurs both between the centrosomes linked by mitotic spindles and between the two centrosomes that are simply adjacent, and four daughter cells are formed
What is sufficient to make cleavage furrow?
2 adjacent centrosomes (don’t need chromosomes)
What is the role of kinetochore microtubules?
connect the chromosomes
What is the role of the overlapping microtubules?
connect with other microtubules which are important for cytokinesis
Push centrosomes away from each other
How does cytokinesis work?
Actin filaments are anchored into the lipid bilayer by cdc43. The actin filaments are connected to myosin filaments. Then the actin and myosin filaments crawl across each other pulling the cdc43 molecules together.
What is the plane of cleavage for cytokinesis?
The cell divides directly through the spindle
What is the idea of rocking spindle? Why is it needed?
The spindle can rock and move in the cell with signaling molecules and astrocells
This changed the orientation of the cell division since it the division in dependent on the location f the spindles (top and bottom or left and right)
Is cleavage patterns depends on the amount of yolk?
Yes
What are the two main types of cleavage patterns?
- Holoblastic (complete) cleavage
2. Meroblastic (incomplete) cleavage
What are the two types of holoblastic (complete) cleavage?
- Isolecithal (sparse, evenly distributed yolk)
2. Mesolecithal (moderate vegetal yolk disposition)
What are the 4 types of isolecithal cleavage?
- Radial cleavage (echinoderms, amphioxus)
- Spiral cleavage (annelids, mollusks, flatworms)
- Bilateral cleavage (tunicates)
- Rotational cleavage (mammals, nematodes)
What is the more specific type of mesolecithal cleavage?
Displaced radial cleavage (amphibians)
What are the two types of meroblastic (incomplete) cleavage?
- Teloecithal (dense yolk throughout most of cell)
2. Centrolecithal (yolk in center of egg)
What are the two types of teloecithal cleavage?
- Bilated cleavage (cephalopod mollusks)
2. Discoidal cleavage (fish, reptiles, birds)
What is the more specific type of centrolecithal cleavage?
Superficial cleavage (most insects) Create a multinucleated structure
Dextral vs. Synistral cleavage?
Dextral = right-handed coiling Synistral = left-handed coiling
At what stage of division does the spiral pattern (dextral/synistral) develop?
8 cell stage
How do the first 5 divisions of sea urchin developments go?
1st division: meridinal
2nd division: meridinal @90 degrees
3rd division: equitorial
4th division: animal = meridinal, vegetal = asymetrical
5th division: animal = equatorial, vegetal = equatorial
What is the maternal to zygotic transition (MZT) marked by (3)?
- Nucleus starts to take control
- Pre mid-blastula > equal coordinated divisions
- Three new events added
What 3 new events are added during the MZT?
- Growth phases return (G1 & G2) (things slow down)
- Synchronicity is lost (divisions are no longer standard/uniform)
- New mRNA is transcripted (z mRNA)
What is mmRNA?
maternal mRNA
The alleles being expressed are from mom
What is zmRNA?
zygotic mRNA
The alleles being expressed are from mom and dad
What is the MZT?
The transition from mmRNA to zmRNA
What is actinomycin?
Blocks transcription
What gene/protein is responsible for targeting mmRNA for destruction?
Smaug
What gene/protein is responsible for activating zmRNA?
Zelda
What are the 5 major stages of the developmental process?
- Zygote
- Embryo
- Morula
- Blastula
- Gastrula
What are micromeres?
They exist at the vegetal pole of the urchin 60 cell stage
SEE END FOR LEC 14 CONTENT
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Division of cells in amphibians goes quickly through the _____ hemisphere and slowly through the _____
animal hemisphere, yolk
Why does division occur more slowly through the yolk of amphibian cleavage?
The yolk is made up of lipids which are difficult to split
What is the grey crescent that develops during amphibian cleavage?
The grey crescent is exposed nonpigmented cytoplasm that forms because of the rotation of the cell cortex after the sperm bind in the animal hemisphere
The grey is the inner grey region underneath the dark black outer cortex of the animal hemisphere
How does the sperm binding cause the creation of the grey crescent in amphibian development?
Microtubules shift at fertilization to organize themselves (50% > 70%) and it causes rotation
What is the role of EP cadherins in amphibian development?
They hold the blastula together
What drives the formation of the ectoderm, mesoderm, and endoderm of the amphibian?
Signaling molecules: Vg1 and VegT
Which structures turn into the germ layers in the amphibian?
Epidermis > ectoderm
Supra-blastoporal endoderm and sublastoporal endoderm > endoderm
Lateral plate mesoderm > mesoderm (inside outer layer)
Talk me through invagination and involution of frog gastrulation
Involution of the grey cresent creates the dorsal blastopore lip > invagination > archenteron (> primitive gut) > bastocoel gets displaced > eventually dissapears. Ectoderm spreads to cover rest of embryo
What are the 4 major cell movements in amphibian development?
- Epiboly
- Vegetal Rotation
- Invagination
- Involution at gastropore lip
Epiboly in amphibian development
Epiboly is the spreading out of cells (going from 3 layers to 2 layers)
How the ectoderm spreads to encompass the whole embryo
Vegetal rotation in amphibian development
Movement of cells that swing upward from the vegetal hemisphere and into the animal hemisphere inside the blastocoel
Invagination in amphibian development
Bottle cells start going inward (invaginating) beginning the initial formation of the blastopore
What are bottle cells?
Wedge-shaped cells at the apical constriction of the amphibian embryo that invaginates to form the blastopore
What is the dorsal blastopore lip graft comprised of?
A collection of bottle cells
What does the dorsal blastopore lip graft do in salamander development?
Migrate inward creating the blastopore groove
This is proof that bottle cells drive invagination
What drives invagination in amphibian development?
Bottle cells
There is more cell division in the _____ hemisphere first in amphibian development.
Animal
What is the spreading out of the ectoderm of amphibian embryo driven by? (3)
- Epiboly
- Cell division
- Fibronectin (ECM protein used for guidance)
What is the neurula?
Formation of neural tube
What is fibronectin used for in amphibian development?
Proper development of the round embryo (see photos)
What are the 3 cell populations that lead the way of involution on the underside of the ectoderm in amphibians?
- Pharyngeal endoderm (forms pharynx = mouth)
- Head mesenchyme
- Chrodomesoderm (notochord)
When does the pattern of placing (fate mapping?) occur first in amphibians?
At the involution of the blastopore lip
Talk me through the development of the lateral, ventral lips, and yolk plug, in amphibians?
The formation goes dorsal lip then lateral lip then ventral lip then when all three of them begin to move in the yolk plug is formed (see photos)
Non-IMZ cells spread out and fill the space left by cells that moved inward
Yes, they do this by convergent extension
What is genetic equivalency?
All the cells in the embryo are the same genetically
What experiment did Hans Spemann conduct to determine genetic equivalency?
He used a baby hair to create a ligature in an 8-cell stage embryo creating two halves : one with out nuclei and one with all nuclei
At the 16-cell stage he relaxed the ligature and allowed 1 nucleus to pop over
At 14 days he had 2 fully developing salamander
The conclusion: A nucleus from a 16 cell stage has everything it needs to make a whole embryo (At the 16 cell stage all the cells have genetic equivalency)
What experiment did Hans Speamann conduct to determine egg asymmetry?
He separated a cell after the first cleavage and either divided it down the middle of the grey crescent or half included the grey crescent and the other half did not. In the end, if he split the grey crescent down the middle he got two salamanders. If he split it so only one had the grey crescent - only the half with the grey crescent half became a salamander, the other became the belly piece
The conclusion: The grey crescent is necessary and important for development in amphibians
Usually, an animal is either conditional or autonomous, but the salamander is unique because ____
The early gastrula contains conditional cells, but
The late gastrula contains autonomous cells
What experiment did Mangold and Spemann conduct to discover the “organizer”?
She dissected a piece of the dorsal blastopore lip/presumptive notochord and transplanted it onto the presumptive epidermis of the blastopore causing abnormal dorsolation creating a second axis of development leading to 2 salamanders developing stuck together by their stomachs
What is the “organizer” in amphibian development?
The organizer is two signals
- Signal to become dorsal
- Signal to become mesoderm from Nieuwkoop center
What is the Nieuwkoop?
The dorsal most stable portion?
Secretes mesoderm-inducing signals in amphibians
What two functions does the blastocoel serve during frog progressive determination?
- Space for cells to move in
2. Separates ectoderm from mesoderm-inducing signals
What does it mean that frog progressive determination is bottom-up?
Vegetal cells > endoderm
Marginal (equatorial cells) > mesoderm
Animal cap cells > ectoderm
If the blastocoel didn’t exist what would happen to the animal cap cells of the frog blastula?
The animal cap would be converted to mesoderm by mesoderm-inducing factors released from the vegetal cells
What does VegT do for amphibian development?
VegT mmRNA > Veg T > Nodal > Eomes > Mesoderm formation
What does Vg1 do for amphibian development?
Vg1 mmRNA > Vg1 > Wnt inbibitor (temporal fashion) > Mesoderm formation
What is the 4 major functions of the organizer?
- Self-differentiate dorsal mesoderm (prechordal plate, chordamesoderm (earliest most dorsal structures))
- Dorsalize surrounding mesoderm > paraxial (somite) instead of ventral
- Dorsalize ectoderm > neural tube
- Initiate gastrulation movements
How does dorsal determination work in amphibians?
During cortical rotation disheveled proteins in the vegetal hemisphere get rotated into the animal hemisphere
Wnt > Frizzled > Disheveled -| GSK-3 -| b-catenin > transcription of siamois and twin proteins (sets up axis of formation) > activates transciption of organizer genes
What is Stripson used for in mammalian development?
An enzyme that digests pore in zona pellusida allowing for hatching
What day does implantation into the uterus occur?
Day 6
What are the 5 pieces the endometrium (outermost layer of the uterine wall) has to allow for implantation?
- Collagen
- Laminin (extracellular structural protein)
- Fibronectin
- Hyaluronic Acid / Hyaluronin
- Heparin Sulfate Receptors
What are the 5 pieces the trophoblast has to allow for implantation?
- Collagenase (breaks down collagen in the uterine wall)
- Laminin Receptors
- Fibronectin receptors
- Hyluronidase (break down hyaluronic acid)
- Heparin Sulfate Receptors
Definition of syncytium
Multiple cells fusing together to form a multi-nucleated structure
What are the 3 main stages of implantation?
- Attachment of blastocyst
- Penetration of uterine wall
- Interaction with maternal blood vessels
What are the 2 layers of the trophoblast?
- Syncytiotrophoblasts (Multi-nucleate)
2. Cytotrophoblasts (mono-nucleate)
What are 2 layers of the bilaminar germ disc (formed from the blastocyst)
- Hypoblast
2. Epiblast
What day does the penetration of the uterine wall by the trophoblast occur?
8 days (3 weeks)
What is the coagulation plug?
Only thing left on uterine wall after complete implantation by the trophoblast
When does the interaction with maternal blood vessels of the trophoblast occur?
9 days
Complete implantation into uterian wall leaving coagulation plut
What is an ectopic pregnancy?
When implantation occurs somewhere else besides the uterus
What are possible places for ectopic pregnancies?
- Fimbrial (in fimbrae)
- Ampullary (in ovaduct near fimbrae)
- Isthmic (in ovaduct near uterus)
- Ovarian
- Interstitial (abdominal cavity)
- Cervical
What is a tubal pregnancy?
If the egg hatches and implants in ovaduct
If the trophoblast hatches too late, where will it implant?
Cervix
What is lithopedion?
When you have interstitial implantation that the mom’s body then recognizes as foreign and wraps in tissue that forms a cyst
Can exist for 40 years unknown by the woman
What are amnioblasts?
Cells that develop into the amniotic cavity
“Where you came from”
What is Heuser’s membrane? How does it form?
Formed when hypoblasts multiply and line the inside of the blastocyst
The lining of the primary yolk sac
What day do the primary yolk sac and extraembryonic coelom form?
Day 10-11
What is the extraembryonic reticulum?
Formed when hypoblasts multiply and secrete ECM
Forms around primary yolk sac
What is the extraembryonic mesoderm?
Encases extraembryonic reticulum
What is the chorionic cavity?
The space inside the extraembryonic mesoderm created after the extraembryonic reticulum breaks down
What day do the chorionic cavity and extraembryonic mesoderm form?
Day 12-13
How does the definitive yolk sac form?
It forms and pushes the primary yolk sac off to the side and creates a new cavity = definitive yolk sac
What day does the definitive yolk sac form?
Day 13
What is the ultimate layout of the embryo at day 15?
You have the syncytiotrophoblasts at an invasive stage on the outside surrounding trophoblastic lacuna.
Next layer is cytotrophoblasts.
Next layer is the extraembryonic mesoderm which lines the chorionic cavity
The connecting stalk, made of extraembryonic mesoderm surrounds the amnionic cavity and definitive yolk dac
The remnants of primary yolk sac are on the far edge of the chorionic cavity
What are some defining characteristics of mammalian cleavage?
- Cleavage pattern is rotational
- Very slow division
- Quickly become asynchronous
- MZT occurs early on
Slow cleavage allows what to take place? How long does the first cell division occur?
MZT
24 hours = 2-cell stage
What happens during compaction?
at the 8 cell stage the embryo cells squish together (do not fuse)
What is the mechanism of compaction?
At the early 8-cell stage, the bonds are non-polar but there are light local contact effects
At the compact 8-cell stage, there is the formation of tight and gap junctions and a greater number of connections are formed which polarizes the cells and squishes the round cells into a triangle shape
Compaction is driven by what two structural proteins?
E-Cadherins & microvilli on the apical outside facing end at the 16-cell stage
How does the inner cell mast inside the blastocyst form?
There is an azymmetrical division in the trophectoderm perpendicular to apicobasal axis
How does the trophectoderm expand?
There is a symmetrical division parallel to the apicobasal axis in the trophectoderm
Inner cell mass gives rise to what?
Embryo proper
There is differential gene expression in blastocyst formation
Yes
Transcription factors allow for activation of trophoblast formation
True
Talk me through the development of the ICM at the molecular level
Increase amount of Hippo (binding molecule between neighboring cells) > activates Lats > phosphorylates Yap > destruction of Yap > release inhibition on Tead4 (which is a transcription factor) > transcription Cdx2
What does the ICM develop into?
ICM > 1. Primitive endoderm»_space; yolk sac
2. Epiblast > amniotic ectoderm & embryonic epiblast > primitive streak
Humans gastrulation includes the development of what structures? (7)
- amnioblast
- amniotic cavity
- bilaminar germ disc
- Primitive groove
- yolk sac
- epiblast
- hypoblast
Primordial germ cells and RBC production
Same order of inward migration
Primitive streak formation forms where during human gastrulation?
Forms in the primitive groove of the epiblast surrounding the amniotic cavity
Cells along the primitive streak migrate in to replace what?
Replace the hypoblast
How does uteroplacental circulation come about (5 steps)
- Trophoblast lacunae form in synctioT
- Maternal sinusoids: lacunae fuse with swelling maternal blood vessels
- Primary stem villus: cytoTs bud into syncytioT (enduced by extraembryonic (ee) mesoderm forming underneath) into lacunae
- Secondary stem villus; ee mesoderm penetrates primary villus
- tertiary stem villus: blood vessels form from mesoderm
Why does the placenta need to be delivered?
Don’t want infection or hemmoraghing
What going into (3) and out of (2) the fetus in maternal-fetal circulation?
Nutrients, oxygen, IgG antibodies into fetus
CO2 and waste out of fetus
The placenta helps “mask” the fetus from mom’s immune system
True
What are the 4 layers that separate fetal and maternal blood?
- Fetal blood vessel endothelium
- Loose CT of villus core
- Cytotrophoblast cells
- Synchytiotrophoblasts
The villus has two intact cell layers, what are they?
Synctiophoblasts
cytotrophoblasts
In the villus interior there are mesenchymal cells with macrophages and fetal capillaries
How does the villus change during the middle third of the pregnancy?
The capillaries migrate to the villus surface
The cytotrophoblast layer disappears slowly and the syncytiotrophoblast layer becomes thinner
What are amniotes?
Vertebrates whose embryos form an amnion (birds, reptiles, mammals)
What is the amnion?
Derived from embryo, surrounds embryo
What are the 4 extraembryonic membranes?
- amnion: surrounds embryo
- chorion: outer layer, makes up fetal portion of placenta
- yolk sac: becomes small and extended out through umbilical chord
- Allantois: part of and forms an axis for the development of the umbilical cord
What is the extraembryonic coelum?
cavity linned by mesoderm
Dizygotic twins
Both eggs implant and have their own trophoblast and inner cell mast and amnionic cavity and placenta
DiDi twins
Single zygote splits at 1-3 days prior to trophoblast formation; 2 blastocysts, 2 trophoblasts, 2 placentas, 2 amnionic cavities
33% of identical twins
MonoDi Twins
Zygote splits after 4-8 days after early blastocyst formation; 2 ICM, 1 placenta, 2 amnionic cavities
66-70% of identical twins
MonoMono twins
Zygote splits after 8-12 days after late blastocyst formation; 1 placenta, 1 amnionic cavity
Very rare
Conjoined Twins
Zygote splits after 13 days after late blastocyst yeilds on ICM; 1 placenta, 1 amnion, 1 chorion
1% of twins
Possibly occurs at gastrulation
What are the 4 types of conjoined twins?
- Craniopagus (heads)
- Parapagous (sides)
- Thoracopagus (stomachs)
- Pygopagus (hip/butt)
If conjoined twins develop at 19 weeks gestation what 2 body systems do they share?
Shared heart Shared bowel (separate bladders)
What does the ICM develop into? What does the trophoblast develop into?
ICM > embryo
Trophoblast > placenta
What is the definition of a stem cell?
Has the ability to make more of itself (stem cells) and to differentiate into new cell types (committed cells)
What are the 4 levels of stem cells?
- Totipotents (can by anything)
- Pluripotent (lots of things)
- Multipotent (multiple things)
- Unipotent (one thing)
What is the ultimate totipotent stem cell?
Zygote
The totipotent stem cell makes which 2 preliminary structures?
- ICM
2. Trophoblast
At what cell stages can you find totipotent stem cells?
2-4 cell stage
Where are pluripotent stem cells found?
Inner Cell Mass
Can develop into anything in the embryo (but not the trophoblast)
Where are multipotent stem cells found?
In the primary germ layers: can make cells within a given germ layer
Can be in embryo or adult (hematopoietic stem cell can form WBCs or RBCs)
What body systems does the ectoderm form? (2)
Epidermis
Nervous system
What body system does the mesoderm form (6)?
Bone Cartilage Kidney Gonad Circulatory system Muscle
What body systems does the endoderm form? (4)
Digestive system
Respiratory system
Pancreas
Liver
Where are unipotent stem cells found?
Found in particular tissues, regenerate a particular type of cell
ex) spermatogonia, skin cells
What are 2 sources of embryonic stem cells?
- In vitro fertilization frozen embryos that are donated
2. Chord blood
What are induced pluripotent stem cells (iPS)?
Taake multipotent stem cells and genetically decode specific genes to get back to the pluripotent stage
What are the 4 characteristics of chordates?
- Dorsal hollow nerve chord
- Notochord
- Phayngeal gill slits
- Pastanal tail
What is chordomesoderm?
Mesoderm that will make notochord
What are the 6 steps to the notochordal process?
- Forms just caudal to precordal plate
- increases as node moves posterior (complete by day 20)
- initally solid but quikcly hallows
- decends inot endoderm
- fuse with endoderm
- emergy back out as a solid chord
What are the 3 fates of ectodermal derivatives?
- Surface ectoderm > skin
- Neural crest cells > lots of things
- Neural plate/neral tube > CNS
What drives the 3 fates of the ectodermal derivatives?
Levels of BMP
- High BMP = epidermal ectoderm
- Med BMP = neural crest cells
- Low/no BMP = neural ectoderm
What are 3 neural plate genes?
Sox 1,2,3
What does Sox 1,2,3 do? (2)
- activate plate genes
2. inhibit epidermal and NCC (neural crest cells) genes by blocking BMPS
When do Sox 1,2,3 cause their effect on plate gene activation?
During the early neurula stage
What are the 2 ways the neural tube forms?
- Primary neurulation
2. Secondary neurulation
What is primary neurulation? (4 stages)
- Elongation and folding of nueral plate
- Elevation of neural folds
- Convergence of neural folds
- Closure of neural tubes
What is secondary neurulation?
Subpopulation of mesenchyme cells > solid structure > hollows out to form tube
How does elongation of neural tube occur?
Convergenct extension and replication
The neural tube folds around what structure?
Median hindge point (MHP)
Anchors along midline to underlying notochord
How does the median hinge point (MHP) form?
the cells become wedge shaped due to induction by notochord
What drives the elevation of neural folds? (2)
Sonic hedgehod (SHH) Driven by pressure on sides by epidermis ectoderm as it moves midline
How does cell wedging occur?
- cells elongate using microtubules
- cell apical shortens using actin filaments
- surface ectoderm movement forces tube formation inward
What is the dorsolateral hinge point (DLHP)? What is it induced by?
Anchored to surface ectoderm - hinge points on the sides (see photos)
DLHP induced by surface ectoderm (noggin blocks BMP because noggin is far enough away from Shh produced by notochord)
During convergence of the notochord the epidermis is determined by what signaling molecules? the notochord/floor plate? DLHP?
Epidermis = high BMP
Notochord/floor plate= high Shh
DLHP = low BMP, low Shh
BMP = antagonistic to hinge point formation
Noggin = direclty blocks BMP function, allowing hinge point to form
What signaling molecule is essential for neural tube closure?
Noggin (inhibits BMP)
What is spinal dysraphism? How common is it? What is it caused by(2)?
When there is a defect in neural tube closure
1 in 1,000 births
Causes: genetic, environmental facts (poor nutriton, drugs, diabetes, obsity, toxins)
What are the 3 types of spinal dysraphism?
- Anencephaly: anterior region does not close properly
- Spina bifida: posterior region does not close properly
- Cranioarchischisis: enter length of tube does not close properly (will result in still born birth)
What are the 3 degrees of spina bifida?
- Spina bifida occulta: vertebrate arch fails to form, tube forms normally
- Meningocele: meninges (dura & arachnoid) extend out gap in spinal verebra but not neural tube
- Meningomyelocele: meninges and neural tube extend out gap in spinal vertebra (much more concerning)
What is anencephaly?
Upper portion of nueral tube fails to develop: don’t have development of regions of hemispheres (75% stillborn or die within days to weeks)
What drives separation of neural tube from the ectoderm?
E-cadherins
N-cadherins
Disruption of either leads to incorrect closure
Where does secondary neurulation occur?
Chick = posterior to hind limbs
Mammals = sacral region
Occurs at posterior regions of embryos only
What are the three levels of brain differentiation?
- Anatomical - chambers (ventricles) of brain plus hollow spinal chord
- Tissue - cells arrange into different function regions of tube wall (ventricular, interned, marginal)
- Cellular - neuroepithelial cells differentiate into neurons and glial cells
What drives brain differentiation?
Brief time areas of the brain close off > increase in CSF > increase in pressure > outpocketing (tel, die, mes, met, mye)
What genes dictate the axis of symmetry / hindbrain spinal chord differentiation?
Hox genes (subgroup of homeobox genes)
Series of genes expressed along anterior-posterior axis of embryo
The position on chromosomes mirrors position on body
What drives dorsal-ventral specification?
2 converging gradients
- High BMP (TGFb family) in roof plate decreasing as you go ventral
- High levels of SHH ventral and decreasing as you go dorsal
What is the functional difference between dorsal and ventral neural tube differentiation?
Dorsal spinal chord = sensory
Ventral spinal chord = motor
Humans keep fetal neural growth rate until what age?
2
Why does the brian have an exponential growth rate much higher than other organ and other organisms?
Added growth must be after birth, otherwise brain/head would be too large to pass through the birth canal
The human head weighs how many pounds?
8 lbs
What are the 5 stages of fetal growth rate of brian in humans?
- Infancy (0-3), ends weaning
- Childhood (3-7), high caloric intake
- Juvinile, feed independence onset of physical maturity
- Adolescence
- Adulthood
At what age do you have a high percent of white matter in the prefrontal cortex?
20
During gastrulation head ectoderm is made competent to respond to eye-inducing diencephalon signals
True
What does Pax6 do during eye development?
Pax6 is critical for ectoderm competence
Prechordal mesoderm and foregut endoderm sends signal to what during eye development
Prechordal mesoderm and foregut endoderm send signal to give head ectoderm lens-forming bias
What produces the signal that activates Pax6 during eye development?
Anterior neural plate
What is the optic cup / lens placode interaction?
Optic vesicle induces lens forming bias
Optic vesicle induces head ectoderm into lens placode
Optic vesicle > optic cup
Talk me through eye development in terms of structures
Prechord/endoderm + presumptive retina > surface ectoderm > presumptive lens placode
Optic vesicle > surface ectoderm (pesumptive lens placode) > lens placode
Lens placode > optic vesicle > optic cup
Optic cup > lens placode > lens vesicle
Lens vesicle > surface ectoderm > cornea
Talk me through eye development in term of signaling for competent and differentiation
- Prechordal mesoderm / endoderm tells diencephalon (presumptive retina) & surface ectoderm (presumptive placode) to be competent
- Presumptive retina > optic vesicle > tells presumptive placode to differentiate into lens placode > lens placode tells optic vesicle to differentiate into optic cup > optic cup tells lens placode to differentiate into the lens vesicle
- Optic cup > retina
- Lens vesicle > lens
- Lens vesicle tells surface ectoderm to differentiate into the cornea
- Has reciprocal inductions
- Has sequential inductions
Talk me through eye field formation including cell signaling molecules
- active Noggin allows for neural induction (formation of neural plate)
12 Noggin -| BMP -| Otx2, making Otx2 active leading to fore/ midbrain specification
- active Otx2 -| Noggin’s signal to ET, making ET active. ET > Rx > Pax6. ET, Rx, Pax6 lead to eye field specification (forebrain > eye field)
- Pax6 leads to the development of the eye from the eye field
What would happen if an embryo developed without Pax6?
There would be no optic vesicle / the optic vesicle would be deformed
Pax6 produces single eye field in center of ventral forebrain
Why is the separation of eye field important?
You only have one eye field during development, to have 2 eyes you need it to seperate or you will only have 1 eye (cyclopia)
What causes the separation of eye field?
Shh -| Pax6
The inhibition of Pax6 allows the split eye fields into 2 eye fields prior to optic vesicle formation
What is human cyclopia?
If the fetus lacks Shh you do not get the inhibition of Pax6 leading to the formation of only one eye
What does overexpression of Shh cause in regards to eye development?
Over expression of Shh results in a complete lack of eye development
This over expression probably resulted because Shh promotes other senses
How do our photoreceptors change from infancy to adulthood?
Babies have large and few photoreceptors (can only see things when they are close to their face)
Adults have thin / tiny photoreceptors but high density (allows us to increase resolution)
Where do neural crest cells (NCC) form?
They form at the border between surface ectoderm and neural plate
What do NCC do after they separate from the neural tube?
Migrate though the body
What are the 4 major types of NCC (neural crest cells)?
- Peripheral Nervous system (neurons, glial cells)
- Endocrine & paracrine Derivatives (epinephrine-producing cells of adrenal gland)
- Pigment-cells of epidermis (melanocytes)
- Skeleton & connective tissue of head
Two sets of signals lead to differentiation of ectoderm into 1 of 4 fates, what are they and how do we get the 4 fates?
Wnt and BMP
- epidermis if Wnt and BMP are expressed continuously
- Placodal (sensory) cells if Wnt expression is followed by BMP with no overlap
- Neural crest cells if Wnt is continuous with delayed BMP expression
- Neural cells if only Wnt is expressed
What is the importance of Sox10 in neural crest cell induction?
Sox10 is critical for NCC specification by binding to enhance numerous target genes (which turn on type-specific ejector genes)
What are 4 regions of neural crest cells (NCC)?
- Cranial: form bones and connective tissue of head region, portions of inner ear, cartilage of upper throat
- Trunk: 2 paths. 1: ventolateral > dorsal root ganglia and sympathetic g. 2: dorsolateral > melanocytes
- Vagal (somite 1-7) / Sacral (>28): parasympathetic nerves of gut
- Cardiac (somite 1-3): form muscle wall of large arteries, septum diving aorta, pulmonary artery)
Trunk nerual crest cell migration (NCC) has two paths, what are they?
- Ventral path: move down the neural tube and cut through the somites and form sensory (dorsal) root and para/sympathetic neurons (white matter)
- Dorsolateral path: migrate between epidermis and dermis above somites and enter ectoderm to form melanocytes
How do dalmations get their spots?
Failure of NCC to migrate / form results in spotted pattern
What 3 cells compose the dorsal root ganglia?
- Posterior somite of adjacent somite
- Anterior somite
- Posterior somite
Trunk NCC (TNCC) migrate through the anterior sclerotome, causing a pattern of what?
A pattern of nerves and no nerves along the spinal chord since the TNCC only leave the spinal chord on the anterior side of the somites
Cranial NCCs have what 2 unique abilities?
- Form melanocytes, neurons, glia (like TNCC)
2. Form cartilage and bone (unlike TNCC)
What gives vertebrate heads their defining feature?
Cranial neural crest cells (NCC)
Talk to me about the migration of cardiac NCC
Come off the first 3 somites > from bulbus cortus septum which separates aorta and pulmonary artery during developing heart
TNCC used to have the ability to produce bones
True
What does mesoderm form?
Forms most organs tissue between ectoderm wall & endoderm epithelia
Includes musculoskeletal, cardiovascular, urogenital
Mesoderm and Endoderm form simultantious with what structure?
Neural tube
What are the 4 regions of the mesoderm?
- Chordamesoderm: forms notochord
- Paraxial (somitic): dorsal (forms parts of bone/muscle/cartilage of back, dermis)
- Intermediate: kidney and gonad (minus germ cells)
- Lateral plate: heart, blood vessels, blood islands, body cavity lining, mesodermal)
What is Tbx6 important for?
Somite differentiation
It blocks signals that say “develop into neural tube”
Tbx6 -| Sox2
Tbx6 -| Pax6
What induces the formation of somites?
Noggin
What are the 3 functions of somites?
- Dictate NCC migration
- Form vertebrae & ribs, dorsal skin dermis
- Back/limb/body wall skeletal muscles
The number of somites vary between species
True
What are the 5 stages of the formation of somites? What signaling molecule corresponds to these changes?
- Fissure formation (Ephrin)
- Periodicity (notch): tells where to cut
- Epithelialization (cadherins): form epithelial around somite
- Specification (Hox)
- Differentiation
Hox gene expression indicates border between what?
Vertebra types (somite type)
Somite fate is dictated by what?
Position
If you take a somate from the thoracic area and transplant it to the cervical area is will differentiate into thoracic area - its original fate (commited?)
What is the traditional view on the compartments of somites?
- Dermamyotome (myotome > skeletal muscle, dermatome > back dermis)
- Sclerotome > vertebral and rib cartilage
What is the current view on the compartments of somites?
- Dermamyotome: Myotome > Lateral edges generate primary myotome the forms muscle. Dermatome > Central region forms muscle, muscle stem cells, dermis, brown fat cells
forms - Sclerotome forms verebral and rib cartilage, dorsal region forms tendons, medial region forms blood vessels and meninges, central mesenchymal regions forms joints
What are the 3 derivatives of somites (what they turn into)?
- Cartilage of vertebrae & ribs
- Muscles of rib cage, limbs, abdominal wall, back tongue
- Dermis of dorsal skin
Somite components again
(1)Sclerotome (ventral-medial)
+ become mesenchymal
+ cartilage/bone of vertebrae & ribs
+leaves 1st from somites
(2) Dermomyotomes (split into two groups
a. Lateral myotomes (2: dorsomedial & ventrolateral)
(1) primaxial: muscles of back & ribs
(2) abaxial - body wall/limb muscles/tongue muscles
b. Dermotome - dermis of back skin w/ ectoderm
What does the sclerotome become?
- Mesenchymal
- Cartilage / bone of vertebrae and ribs
Leaves 1st
What does the dermomytome become?
2 groups
- Lateral myotomes (primaxial > muscles of back and ribs, abaxial > body wall/limb muscles / tongue muscles)
- Dermotome > dermis of back skin with ectoderm
Somite patterning comes from signalling molecules, what signalling molecules cause the formation of sclerotome, paraxial dermmyotom, dermatome, and abaxial dermamyotome?
Sclerotome: Shh from notochord and floor plate
Pariaxial dermamyotome: Wnt/NT3 from roof plate and low Shh from notochord
Dermatome: Wnt/NT3 from roof plate and Wnt from epidermis
Abaxial dermamyotome: Wnt from epidermis, BMP/ FgF from lateral plate
What are the 4 main steps to muscle formation?
- Myoblast cell division (FGFs induced)
- Cells align via cadherins adhesion
- cell-cell fusion (meltrin induced)
- Interleukins recruit other myoblast to fuse
Vertebrates are created from part of __ somites
2 seperate A - Rostal segment B - Caudal segment A - Rostal segment B - Caudal sement B+A = vertebrae
How are the kidneys formed?
Signals from the paraxial mesoderm induce pronephros formation in the intermediate mesoderm
What are the 3 stages of kidneys in embryo?
- Pronephric
- Mesonephros
- Metanephros
What are the 6 steps of metanephric formation?
- Formation of metanephric mesenchyme and ureteric bud – Wnt & FGF/RA differential expression induces formation from intermediate mesoderm
- Mesenephric mesenchyme induces outgrowth of ureteric bud
- Ureteric bud prevents mesenchymal apoptosis
- Mesenchyme induces branching of ureteric bud
- Wnt signals convert the mesenchyme cells into nephron
- Insertion of ureter into bladder
Reciprocal induction
What is the cloaca?
Forms an opening into allantois
What is the urorectal septum?
Divides cloaca into rectum and urogenital sinus
What is the ureter?
Attached to cloaca
What is the urogenital sinus?
Forms bladder at anterior end
Forms urethra at posterior end
The lateral plate splits in 2 horizontally, what two domains?
- Somatopleure: somatic mesoderm + ectoderm (dorsal)
2. Splanchnopleure: splanchnic mesoderm + endoderm (ventral)
What is the coelom of the lateral plate?
Cavity completely lined by mesoderm
Between somatopleure and splanchnopleure
The coelom is divided into what 3 regions?
- Pleural (thorax)
- Pericardial
- Peritoneal (abdominal) cavities
What are the 3 major sources of bones?
- Somites: axial skeleton
- Lateral plate mesoderm: limb skeleton (apendicular)
- Cranial neural crest cells: branchial arches, craniofacial bones
What are the 2 main pathways of bone formation?
- Direct ossification (mesenchymal cells to bone) = bones of extremities & weight bearing axial skeleton
- Endochondral ossification (mesenchyme > cartilage > bone) = flat bones of skull and face, mandible, clavicle
Osteocytes
build bone
Osteoclasts
breakdown bone
Talk me through intramembranous ossification
Mesenchymal cells cluster – Primary ossification center
+cell round up and form osteoblasts (secrete matrix)
+calcification follows (Osteoblasts trapped in matrix become Osteoclasts)
Chondrocytes come together > cartilage skeleton > cartilaginous breakdown > blood comes in > brings in osteoblasts > cartilage is replaced by bone
Epiphyseal growth plate
On the end of bones where growth comes from (plate in kids, line in adults)
What is the signalling pathway for cardiogenic mesoderm?
A. Wnt(neural tube) -> lateral plate mesoderm => blood and blood vessels. (Lower pathway)
B. Anterior body: Wnt inhibitors ( from pharyngeal endoderm) prevent Wnt lower path
- allowing later signals (BMP, Fgf8) to convert lateral plate mesoderm => cardiogenic mesoderm.
- BMP also important hematopoietic (blood, blood vessel) mesoderm.
C. Center body: Noggin & Chordin (notochord) block BMPs
Thus, cardiac & blood-forming fields not from in embryo center of the embryo.
Signals from pharyngeal endoderm and notochord induce cardiogenic mesoderm formation
True
What does tinman / Nikx do?
- Induces heart cell migrtion (help of FGF heartless gene)
2. Cardiac cell differentitation
Every individual’s circulatory system is slightly different in microvasculature
True
Vasculogenesis
de novo synthesis of blood vessels from lateral plate mesoderm
Angiogenesis
remodeling and pruning into distinct capillary beds, arteries, veins
What are the two main sources of endoderm?
- Visceral from yolk sac
2. Definitive from primitive streak
What are the 2 functions of endoderm?
- induce formation of several mesodermal structures (notochord, heart, blood vessels, mesodermal germ layer)
- Lining of digestive and respiratory tracts
Talk me through the development of endoderm starting at epiblast
Epiblast > high [nodal] > mesendoderm > nodal > definitive endoderm > sox17 > 1. high [BMP/ FGF/ Wnts] = midgut and handgun
- mid [BMP/ FGF/ Wnts] = posterior foregut cells (PFG) > liver, pancreas precursors
- Low [BMP/ FGF/ Wnts] = anterior foregut cells (AFG) > lung, thyroid precursors
Endoderm starts as flat sheet that folds into 2 tube that move towards each other
True
The lateral sides of endoderm form what 2 structures?
Foregut (AIP)
Hindgut (CIP)
At day 21 the oral plate breaks down to form what?
Oral opening
There is only endoderm and ectoderm, no mesoderm
similar interaction in anorectal junction
What are the 4 pouches of the pharynx?
- Auditory canal & eustachian tube
- tonsil’s wall
- Thymus (T lymphocytes), 1 precursor parathyroids
- 2nd precuror parathyroids (lungs at pharyngeal floor between 4th)
Teeth and major salivary glands and anterior taste buds arise from what?
ectoderm
Posterior taste buds, posterior salivary and mucus arise from what?
Endoderm
The pituitary gland is formed from 2 ectoderm interactions, what are they?
- Roof of oral region (rathke’s pouch (glandular portion - anterior))
- Floor of diencephalon (infundibulum (neural - posterior))
The intestines frow outside of the main abdominal cavity and eventually drop back into the body cavity proper because there isn’t room for all the intestines uncoiled in the embryo
True
The allantoise forms what 2 structures?
- Blood vessels
2. Bladder
How does the digestive tract differentiate?
Wnt > intestine epithelium > fine tuned by Hox genes
Barx1 -| Wnt > stomach epithelim
On day 30 accessory structures of the digestive tract develop (3)
- Liver
- Pancreas
- Gallbladder
How does the pancreas develop?
Starts as 2 buds (ventral pancreatic bud and dorsal pancreatic bud) > ventral swings to other side of duodenum > ventral becomes main pancreatic duct, dorsal becomes bulk of pancreas
How is the liver formed?
26 day embryo
Cardiogenic mesoderm -| ecotderm & notochord signaling (which are inhibiting other genes), so cardiogenic mesoderm is blockign the inhibition > hepatic region of gut expresses alpha-fetoprotein and albumin > liver
How doe the dorsal and vental portions of the pancreas come about before they merge?
Aorta sends signals > dorsal pancreas
Right vetelline vein > Pdx > ventral pancreas
Notochord promotes prancreas formation
heart inhibits pancreas formation
Shh expressed entire gut except pancreas region (notochord inhibits shh) which allows blood vessels to induce pancreas genes
What is the respiratory diverticulum (laryngotracheal groove)
Diverticula off pharynx
grows down > differentiates into lungs and trachea because of neighboring cells
What signaling molecules helps separate the trachea and esophagus?
Wnt + no Barx1 > respiratory
Barx1 + no Wnt > esophagus formation
What are the 4 types of tracheoesophageal fistulas?
- Atretic segment in esophagus = food to lungs
- Atretic sgment in esophagus + blind esophageal pouch = food has no where to go + air into stomach
- Atretic segment in esophagus but 2 connections to trachea
- No atretic segment + fistula = food in lungs, air in stomach
What are the 3 modes of branching?
- Domain branching (buds coming off length)
- Planar bifurcation (tips of lobe split at midline, each branch point occuring along same anterior-posterior plane
- Orthogonal bifurcation (later forming branches, bifurcate at tips but at 90 rotation between each branch in alternating pattern)
How does the branching of respiratory system occur?
Smooth muscle forms at tip of branch and connects with smooth muscle around circumference of base > contraction causes split > branch forms
How many lobes do the lungs have? On each side?
5 total
3 on left
2 on right
What are the 5 ways the lungs prepare for birth?
- Defenses up (mucus) against bacteria etc
- Alveoli increase in number (increases surface area)
- Alveoli walls thin
- Surfactant production begins
- Increase in vasculature
What is one of the last systems to develop?
Respiratory system
What do surfactants do? When do they begin developing?
- decrease surface tension to allow for gas exchange
- lungs don’t stick together when air is gone
Develop at 34 weeks, massive release at birth
What is the role of b-catenin in urchin development?
Accumulation of b-catenin in the vegetal cortex and in the micromeres > vegetal cells
If b-catenin is block, the vetetal cell fates are not specifid, and the entire embryo develops as a ciliated ectodermal ball
What is the role of disheveled in urchin development?
- localized to vegetaal cortex prior to 4th division (micromere formation)
- prevents b-catenin degradation in micromere and Veg2
- enters nucleus and combines with TCF
What is the pathway of Wnt and b-catenin? (urchin)
Wnt binds to frizzled > disheveled -| GSK > b-catenin released from APC complex > b-cantenin binds to TCF > activate transcription
How are micromeres formed in urchin development?
Maternal factors
Otx/ b-catenin»_space;> transcription factors activating skeleton-forming genes
How are Veg2 macromeres formed during urchin development?
Transcription factors activating skeleton-forming genes are inhibited
Activation of Notch > non-skeletogenic mesenchyme genes
What are 6 characteristics of gastrulation (urchin)?
- Exterior cells migrate to interior and form ecto, meso, and endoderm
- Cell divisions slow
- New proteins produced
- Archenteron formed
- Growth insignificant
- Blastopore established
What are the 5 stages of urchin gastrulation?
- Primary mesenchyme movement
- Initial archenteron formation
- Secondary mesenchyme movement
- Archenteron elongation
- Stomatodeum fomation
Primary mesenchyme movement
Epithelial-mesenchyme transition
Form skeletogenic cells
What are the 3 units of the primary mesenchyme regression?
- Hyaline layer
- Cell-cell adhesions
- Basal lamina lining blastocoel
How is the positioning of skeletogenic mesenchyme cells determined (urchin)?
FGF signaling and high b-catenin conc
The primary mesenchyme form what?
Syncytial ring
Specific position on animal-vegetal axis
What are the two mechanisms for invagination (urchin)?
- Cell shape change (bottle cells - apical ends contract, basal pushed outward)
- ECM change
1st cells to invaginate inward will later ingress to become the secondary mesenchyme (non-skeletal)
What are the two layers of hyaline (urchin)?
- Inner layer: fibropellin protein secreted during CG reaction
- Outer layer: hyaline
How does invagination of the archenteron happen (urchin)?
Vegetal plate cells secrete CSPG (chondroitin sulfate proteoglycan) > water rushes in > outer layer remains stiff > region buckles
What is secondary mesenchyme pulling? (urchin)
only seen in some specious
secondary mesenchyme form at tip of archenteron and extend filopodia to blastocoel well
Helps with invagination of the blastopore
What is secondary archenteron elongation? (urchin)
Completed by convergent extension
How does stomadeum formation work?
L14 slide 34
skeletal rods extend from anus past mouth region
Where does the embryo develop?
The amniotic cavity
What are 4 extraembryonic structures? (chick)
- Chorion (bird = outer membrane between shell and embryo, human = fetal portion of placenta)
- Amnion: amniotic cavity > surrounds embryo, filled with amniotic fluid
- Yolk sac: birds = contain nutrients (decreases with time)
- Allantois: takes up waste generated by embryo (increases with time)
What does the chalaza do? (chick)
Keeps yolk in center
What is the albumin? (chick)
The egg white
Air space between the inner and outer membrane for agas exchange
What is the marginal zone (chick)?
Where pellucida and opaca meet
Runs along entire basltodisc
How do hypoblast islands form? (chick) (primary hypoblast)
Delamination of cell clusters into subgerminal become hypoblast islands
What is Koller’s sickle (chick)?
Forms right on posterior marginal zone
Specialized thickening cells in epiblast
What do the hypoblast islands do the finish the formation of the primary hypoblast? (chick)
Cells extend from the posterior marginal zone to create the hypoblast
The space between the hypoblast and epiblast is what? (chick)
Blastocoel
The secondary hypoblast begins at _____ and expands forward
Koller’s sickle region
How is the primitive streak formed? (chick)
Signal generated telling epiblast to differentiate into primitive streak
Narrowing extension of cells
Primitive streak extends out ___ into embryo
2/3rd
Primitive groove function
Allows cells to enter primitive streak