004 + 005 introduction to mammalian development and ourselves before birth Flashcards
at how many days does an embryo become a fetus?
56 days (after neurulation)
what are the many embryonic stages/processes to becoming a fetus?
- zygote
- cleavage divisions
- morula (16 cells)
- blastocyst (hypoblast and epiblast = bilaminar disc)
- implantation and gastrulation (ectoderm, mesoderm, endoderm = trilaminar disc)
- axis elongation and morphogenesis e.g. neurulation, limb bud elongation…
how many fertilisations roughly last 56 days when the embryo becomes a fetus?
50%
where is the oocyte/egg released from and where is it caught?
- released from the ovaries
- caught by the fimbriae of the oviducts
where does fertilisation occur?
- in the ampulla region of the oviduct
what happens after fertilisation before reaching the uterus?
- fertilised egg (zygote) undergoes cleavage divisions until it reaches 16 cells when it is called morula
- all while moving through the oviduct towards the uterus
what happens to the embryo once it has reached the uterus, before implantation?
- further cleavage divisions to form a blastocyst (58 cells) made up of the inner cell mass and trophoblast
- then it hatches from the zona pellucida and eventually implants into the wall of the uterus
at how many days does the embryo form a morula, blastocyst and implants into uterine wall?
- morula = 3 days
- blastocyst = 4 days
- implants = 6 days
what is a morula?
- 16 cell ball of identical cells
what is a blastocyst?
- 58 cell ball made up of the inner cell mass ( which will form the embryo/fetus) and the trophoblast (outer membrane)
what does the trophoblast form?
- syncytiotrophoblast and cytotrophoblast
- both act as an outer membrane of the embryo and help with implantation
- also contribute to the chorion (embryo’s contribution to placenta)
what does the inner cell mass form?
- the cells that will be the embryo/fetus
- becomes the bilaminar disc of epiblast and hypoblast
what does the hypoblast form?
- extraembryonic endoderm of yolk sac
what does the epiblast form?
- extraembryonic mesoderm (vasculature)
- amniotic membrane
- trilaminar disc of ectoderm, mesoderm and endoderm which form the fetus
describe the Hippo/YAP signalling to instruct first cell fate of trophoblast
- cells on the outside of the morula are apical
- the apical complex inhibits the Hippo pathways which disinhibit YAP in the nucleus
- YAP activation causes expression of prescription factors CDX2 and GATA3 which causes the cells to become trophoblasts
describe the Hippo/YAP signalling to instruct the first cell fate of inner cell mass
- cells on the inside are not apical so there is not apical complex
- so the Hippo pathway is not inhibited to Hippo inhibits YAP so it is not in the nucleus
- so nucleus can now express transcription factors SOX2, NANOG, OCT4 to become inner cell mass cells
How does the morula form a blastocyst with a blastocoele?
- there is a tight continous apical domain/band that run around the edge of the morula
- whereas there are sparser, weaker cell-cell junctions on the inside of the morula
- Hippo/YAP pathway help creat further apical divide by expressing different transcription factors to form trophoblast and inner cell mass
- blastocoele forms by trophoblast cells pumping Na ions into centre drawing in water
what is the source of embryonic stem cells?
- inner cell mass
at what stage is the embryo totipotent for stem cells?
- from zygote until mid-blastocyst
what does totipotent mean?
- can become any type of cell e.g. can make embryo and extra-embryonic membranes
at what stage is the embryo naive pluripotency?
- from early blastocyst to implantation
what does naive pluripotency mean?
- can make a whole organism when injected into a blastocyst
at what stage is the embryo primed pluripotency?
- from implantation onwards
what does primed pluripotency mean?
- can make any mature cell type but do not contribute to forming an entire new organism when injected into a blastocyst
describe how iPSC (induced pluripotent stem cells) work
- any cell in the body can be reverted into a pluripotent stem cell state by forced expression of Yamanaka factors
- iPSCs can also be self renewable so they can produce lots of copies of themselves to mature into different cell types
what transcription factors code for epiblast and hypoblast?
- Fgf4 = epiblast
- Fgfr2 = hypoblast
what is gastrulation?
-cell movement and ingression to convert the bilaminar disc (epiblast and hypoblast) into the trilaminar disc (ectoderm, mesoderm, endoderm)
what is the primitive node?
mound of cells that appear at the rostral end of the primitive streak on day 15
- the node moves anterior to posterior as gastrulation occurs
- the node is an organiser of the embryo development
- cells that ingress through the node form axial mesoderm
what is the primitive streak?
- a ridge that appears in caudal epiblast on day 14, first sign of gastrulation
- epiblast cells ingress through the primitive streak to form the trilaminar disc
- it establishes bilateral symmetry
describe the process of gastrulation
- a ridge appears in the caudal epiblast layer on day 14 (primitive streak) and on day 15 a mound of cells forms at the rostral end (primitive node)
- epiblast cells ingress through the primitive streak and node
- the first cells to ingress form endoderm cells, second form mesoderm cells and last form ectoderm
- this forms the trilaminar disc of the 3 germ layers which go on to develop into the fetus
what is the overall changes from the trilaminar disc to the neural tube?
- the neural plate forms from the ectoderm (top layer), with neural crest cells in between the epidermis ectoderm and neural ectoderm
- the neural plate folds around the neural groove until it eventually forms a solid tube called the neural tube
- the mesoderm around the neural tube forms somites and the notochord
- the endoderm forms a layer at the bottom of it all
what does surface ectoderm form (above neural tube)
- epidermis of skin
what does neural ectoderm form?
neural tube and neural crest
what does the neural tube form?
the brain and spinal cord
what do neural crest cells form?
- head mesenchyme and the PNS
what does paraxial mesoderm form?
somites
- dermis
- tendons/ligaments
- skeletal muscle
- cartilage
- bone
what does intermediate mesoderm form?
- kidney
- lower urinary tract
- reproductive system
what does the lateral plate mesoderm form?
- adipose
- blood
- endothelium
- lymph
- smooth muscle
- heart
- limb
- spleen
what does the endoderm form?
- gut tube
- thymus
- lung
- pancreas
- prostate
- liver
- thyroid
how is left and right polarity established in an embryo?
- it is established by ciliary beating producing a nodal gradient in the node
- movement (e.g. moving left to right) moves the cilia in the same direction which activates and inhibits different factors which tell the cell which side of the midline they are on and produces a nodal gradient in the node
give an example of what happens if there is a mutation that impairs left/right determination
- situs inversus
- the organs in the body are on the opposite side
- e.g. stomach on the right, heart more towards the left
- can cause complications, mostly during surgery
what is the signalling that conveys direction in the plane of the tissue?
- planar cell polarity
- signalling between cells is the Celsr, Fz and Vangl pathway, however it is inhibited within the cell
- this means that the cells can only have one direction on plane in the tissue, e.g. lateral to medial or anterior to posterior
give an example of what loss of planar cell polarity can cause
- craniorachischisis
- failure of closure of entire neural tube
describe the polarity neural crest cells undergo
- neural crest cells gain front/back polarity as they undergo epithelial-to-mesenchymal transition (EMT)
- the epithelial are interconnected and migrate together
- however some cells undergo EMT and form mesenchymal cells which can migrate alone e.g. to form facial mesenchyme, PNS…
give 4 examples of neural crest dysfunction diseases (neurocristopathies)
- Treacher collins syndrome (affect facial bones and muscle formation)
- Waardenberg syndrome (affect melanocytes (pigmentation) and hearing loss
- charge syndrome (heart defects, growth/genital defects, vision and hearing problems)
- Hirschsprung’s disease ( no nerve cells migrate to the gut, no enteric nervous system)
describe the morphogens pattern in the neural tube
- BMP/Wnt are expressed at the dorsal side
- Shh is expressed at the ventral end
- the varying concentration gradient of these morphogens lead to different transcription factor expression leading to different cell differentiation
what is the signalling protein that causes anterior limb population?
- Irx3/5
what is the signalling pathway that causes posterior limb population?
- Shh –> Gli1 –> target genes
-Gli1 is inhibited by GLi3 - Shh also inhibits anterior limb population growth
what do Shh pathway mutations cause?
- polydactyly and syndactyly
what causes polydactyly and syndactyly that is not due to mutations?
- fetal valproate syndrome ( due to mother taking sodium valproate whilst pregnant (anti-epileptic drug)
what are Hox genes?
Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals.
describe the structure/function of Hox genes
- 4 clusters (A to D) and up to 13 members per cluster
- members at the 3’ end of the chromosome are expressed earlier/more anteriorly than those at the 5’ end
- all have a DNA-binding homeobox domain which activates some genes and represses other
- determines body axis
describe how embryos grow anterior to posterior
- embyros grow in a head to tail direction
- anterior structures develop earlier than posterior ones
- e.g. forelimb forms before hindlimb
describe the Hox gene specifying the vertebral fate
- Hox 5 = cervical spine
- Hox 6-9 = thoracic spine
- Hox 10 = lumbar spine
- Hox 11-13 = sacral and caudal spine
what happens if there is a Hox 10 loss of function?
- causes the lumbar spine to develop into rib-bearing thoracic vertebrae
what happens if there is a Hox10 gain of function?
- causes thoracic vertebrae to develop into lumbar vertebrae, thus having no ribs
describe how somites undergo regional differentiation to form different tissues
- somite cells close to the notochord form sclerotome (forms skeletal vertebrae)
- the closest somite cells to the epidermis form the dermatome
- the middle layer forms myotome
(Shh increases sclerotome formation ventrally, Wnts inhibit sclerotome formation dorsally and increases dermomyotome formation dorsally, BMP inhibits sclerotome and induces dermomyotome formation)
describe vertebral development in embryos
- each sclerotome splits into rostral and caudal segments
- as spinal nerves grow toward rostral somite to innervate myotome, rostral segment recombines with caudal segment of next rostral segment to form vertebral rudiment
- this allows muscle cells to connect to 2 adjacent vertebrae for movement
- called resegmentation
what does the notochord become?
- nucleus pulposus of the intervertebral disc
describe the formation of vertebral discs in embryos
- when sclerotome splits (rostral and caudal), cells remaining in plane of division join to form annulus fibrosus of intervertebral disc
- notochord cells enclosed by this structure differentiate to form nucleus pulposus of disc
- other regions of notochord degenerate
describe the ‘tempo’ of somite formation
-somites form predictably at a set interval
-somites are added at the end of a periodic activation of signalling (FGF/WNT)
- if below FGF/WNT gradient threshold concentration = cells form somite, if above do not = segmentation
- the tempo of the somite segmentation clock is determined by organism-specific rate of biochemical reactions
explain how biomechanics is used by embryos in their development
- the embryonic cells need to work together to change the shape of their tissues
- for example using mechanical forces to fold and close the neuropores of the neural tube
explain how mutation can cause spina bifida in only 1 of the monozygotic twins
- if a mutation occurs during the cleavage divisions ( post the fertilized egg has split into 2 embryos)
- so only 1 embryo will get the mutation (e.g. mutated Vangl2 causing spina bifida) and if the mutation occurs early enough and enough cells carry the mutation, then the baby will develop spina bifida
