early foetal development

Question 1

how do we measure time in embryo-foetal development?

Answer 1

fertilisation age - from ovulation +1

gestational age - from beginning of last period

carnegie age - based on embryological features

or dividing into stages based on development

Question 2

what is fertilisation age?

Answer 2

measured from the time of fertilisation
assumed to be +1 day from last ovulation (fertilisation generally has to occur in this window)
difficult to know exact time of fertilisation unless IVF
usually expressed in weeks post ovulation or days post ovulation
not particularly practical

Question 3

what is gestational age?

Answer 3

calculated from the time of the start of the last menstrual period

determined by fertilisation date (+14 days) if known, or early obstetric ultrasound and comparison to embryo size charts

(it is always 14 days longer than fertilisation age)

Question 4

what is carnegie age?

Answer 4

23 stages of embryo development based on embryo features not time

allows comparison of developmental rates between species

covers the window of 0-60 days fertilisation age in humans

Question 5

what are the stages of embryo development used in measuring time in embryo foetal development?

Answer 5

1. embryogenic stage
2. embryonic stage
3. fetal stage

1 and 2 are in the 1st trimester ( first 12 weeks)

3 is second and third trimester

so embryo becomes foetus at roughly the end of the first trimester

Question 6

what is the embryogenic stage?

Answer 6

1-14/16 days post fertilisation

establishing the early embryo from the fertilised oocyte

determining two populations of cell types:
pluripotent embryonic cells (contribute to foetus)
extraembryonic cells (contribute to the supporting structures eg. placenta)

Question 7

what is the embryonic stage?

Answer 7

16- 50 days post fertilisation

establishment of the germ layers and differentiation of tissue types

establishment of the body plan

Question 8

what is the fetal stage?

Answer 8

50 - 270 days post fertilisation

major organ systems now present but not in the right place

migration of some organ systems to final location

extensive growth and acquisition of fetal viability (ability to survive outside the womb)

Question 9

what happens in the first few days of life?

Answer 9

ovulated oocyte (1 cell) ->

fertilisation with sperm (2 cells)->

becomes zygote (one cell) ->

cleavage divisions to become cleavage stage embryos (2-8 cells) ->

further mitotic divisions to form morula (16+ cells) ->

blastocyst (200-300 cells)

during this process the embryo is migrating along the fallopian tube so it can reach the uterus and implant

zona pellucida is present in all of these stages

Question 10

what is the maternal to zygotic transition?

Answer 10

first major developmental event

occurs at the 4-8 cell stage
UNTIL this stage the genes of the embryo are not transcribed

the embryo is dependant on maternal mRNAs and proteins to get through the first divisions

these mRNA and proteins are synthesised and stored during oocyte development (pre ovulation)

failure to synthesise, store or interpret these during oogenesis can impair embryonic development

in the maternal-to-zygotic transition:
transcription of embryonic genes (zygotic genome activation)
increased protein synthesis
organelle (mitochondria, golgi) maturation

Question 11

what is compaction?

Answer 11

the second major developmental event

starts formation of the first two cell types

around the 8 cell stage or later

outer cells become pressed against the zona pelllucida
the change from spherical to wedge shaped
outer cells connect to each other through tight gap junctions and desmosomes
this forms a barrier to diffusion between the inner and outer embryo
the outer cells become polarised

compacted morula:
has two cell types - inner and outer

later these will develop further in the blastocyst, with the outer cells forming a shell and the inner cells forming a clump at one end of the blastocyst

Question 12

what are the cells present in the early blastocyst?

Answer 12

inner cell mass:
pluripotent embryonic cells that will contribute to the final organism

trophectoderm (cells round the outside):
extra-embryonic cells that contribute to the extraembryonic structures that support development

blastocoel:
fluid filled cavity formed osmotically by trophobalst pumping Na+ ions into cavity

these are enclosed in the zona pellucida:
inhibits polyspermy
protects the early embryo

Question 13

what is hatching?

Answer 13

occurs around day 5-6

the escape of the blastocyst from the zona pellucida
this allows the blastocyst to implant

happens via:
enzymatic digestion
cellular contractions

this leaves the empty zona pellucida

this is vital for the blastocyst to implant

Question 14

what happens during peri-implantation events?

Answer 14

around day 7-9

embryo has undergone initial connection with the endometrium

the trophectoderm (outer cells) lineage separates further: 
trophoblast cells fuse to form syncitiotrophoblast

sincitiotrophoblast invasion destroys local maternal cells in the endometrium

this creates interface between embryo and maternal blood supply

cytotrophoblast cells remain individual to provide a source of syncitiotrophoblast cells

inner cell mass:
epiblast - from which the fetal tissues will be derived

hypoblast - which will form the yolk sac (extraembryonic structure)

Question 15

what are the lineages of embryonic cells by about day 9?

Answer 15

morula ->
splits into inner cell mass and trophoblast

inner cell mass ->
epiblast and hypoblast

trophoblast ->
cytotrophoblast and syncitiotrophoblast

Question 16

what is bi-laminar embryonic disc formation?

Answer 16

day 12+

the bilayer embryonic disc is the final stage before gastrulation

the syncitiotrophoblast continues to expand into the endometrium

some of the epiblast cells become separated from the epiblast by the formation of a new cavity - the amniotic cavity

these amnion cells will contribute to the extra-embryonic membranes

this leaves a two layer disc of epiblast and hypoblast, sandwiched between cavities (amniotic and blastocoel)

the embryo is now ready for gastrulation

Question 17

what does the syncitiotrophoblast do during formation of the bi-laminal embryonic disc?

Answer 17

secretes hCG

detection of beta hCG subunit in blood/urine is basis of pregnancy testing

Question 18

what is the process of gastrulation?

Answer 18

when the three germ layers are created

formation of the primitive streak defines head and tail and left and right axes of the embryo

invagination of cells into the primitive streak forms 3 germ layers:

endoderm - first through streak (where the hypoblast cells were)

mesoderm - sandwiched between endo and ecto

ectoderm - remains on the upper, ventral surface (where the epiblast cells were)

Question 19

what are the embryonic cell lineages after gastrulation?

Answer 19

morula ->
forms inner cell mass and trophoblast

trophoblast ->
form cytotrophoblast and syncitiotrophoblast

inner cell mass ->
forms epiblast and hypoblast

epiblast ->
forms ectoderm, mesoderm and endoderm

Question 20

what body parts does the endoderm give rise to?

Answer 20

GI tract

liver, pancreas

lungs

thyroid

Question 21

what body parts does the ectoderm give rise to?

Answer 21

CNS and neural crest

skin epithelia

tooth enamel

Question 22

what body parts does the mesoderm give rise to?

Answer 22

blood (endothelial cells, red and white blood cells)

muscle (smooth, skeletal, cardiac)

gonads, kidneys and adrenal cortex

bone, cartilage

Question 23

what is notochord formation?

Answer 23

day 13+

notochord is a rod like tube structure formed of cartilage like cells

it forms along the embryo midline, under the ectoderm

grows from the head end of the primitive streak towards the head end of the embryo

it acts as a key organising centre for embryonic development, providing growth factor signals for:
neurulation (CNS formation)
mesoderm development

Question 24

what is the neural plate?

Answer 24

how the notocord organises neurulation

it is an area of ectoderm that sits on top of the embryo.
signals from the notocord below the ectoderm, move up through the embryo and direct the neural plate to form something called the neural tube

Question 25

what is first part of neurulation?

Answer 25

around day 14/15

forming the neural tube and CNS

the notocord sends signals to the neural plate to do two things:
1. for part of the neural plate to invaginate and move down towards the notocord, creating the neural groove

2. for two areas of the neural plate to move upwards, crating two crests, called the neural fold. these are ridges that run along the cranial caudal axis of the embryo
   within the neural folds are neural crest cells

Question 26

what is the second part of neurulation?

Answer 26

a couple of days later (16/17)

the neural folds move upwards and towards each other
they will eventually meet in the middle and fuse
this creates a sealed lid over the top of the neural groove. this forms the neural tube (originally made from neural plate)
this is overlaid with epidermis (ectoderm)

the neural crest cells also migrate, forming folds

Question 27

when does the neural tube close?

Answer 27

has to close for further neural development to proceed

closure at head and ~day 23

closure at tail end ~ day 27

the closure at head end precedes formation of brain structures

Question 28

what happens if the neural tube fails to close?

Answer 28

anencephaly:
absence of most of skull and brain
arises from failure to close at the head end
1/10000 births

spina bifida:
open neural tube at birth
usually open in lower spine due to failure to close tail end
varying severity
0.4-5/1000 births

Question 29

what are neural crest cells and their types?

Answer 29

ectoderm derived
highly plastic and highly migratory, to throughout the embryo

can be classified according to where they end up:
cranial NC - cranial neurones, glia, lower jaw, middle ear bones, facial cartilage
cardiac NC - aortic arch/pulmonary artery septum, large arteries wall musculoconnective tissue
trunk NC - dorsal root ganglia, sympathetic ganglia, adrenal medulla, aortic nerve clusters, melanocytes
vagral and sacral NC - parasympathetic ganglia and enteric nervous system ganglia

defects of neural crest migration/specification lead to diverse birth defects:
eg. pigmentation disorders, deafness, cardiac and facial defects, failure to innervate the gut

Question 30

what is somitogenesis?

Answer 30

formation of somites:
arises from paired blocks of paraxial mesoderm flanking the neural tube and notochord

blocks of paraxial mesoderm condense and bud off in somite pairs, on each side of the neural tube

somitogenesis commences at the head end and progresses down the long axis of the embryo

rate of budding or appearance of somite pairs and number of pairs is species specific
humans: 1 pair/90 mins, 44 pairs

Question 31

what are somite derived tissues?

Answer 31

somites initially form two types of embryonic tissue:
sclerotome - vertebrae and rib cartilage

dermomyotome - sub divides more:

dermatome: gives rise to the dermis of the skin, some fat and connective tissues of neck and trunk
myotome: forms the muscles of the embryo

Question 32

how does formation of the Gut tube work?

Answer 32

happens at day 16+

arises from the yolk sac, which is derived from hypoblast

the primitive gut arises from 2 types of folding in the embryo:
ventral folding - where the head and tail ends curl together
lateral folding - where the two sides of the embryo roll

this pinches off part of the yolk sac to form the primitive gut

primitive gut is then patterned into foregut, midgut and hindgut

Question 33

what are the derivatives of the primitive gut?

Answer 33

(endoderm derived structures)

foregut:
oesophagus, stomach, upper duodenum, liver, gall bladder, pancreas

midgut:
lower duodenum, jejunum, ileum, ascending colon, first two thirds of transverse colon

hindgut:
last third of the transverse colon, descending colon, rectum and upper anal canal

Question 34

how is the heart formed?

Answer 34

mesodermal derived

begins as tube of mesoderm around day 19

beating and pumping of blood begins around day 22

foetal heartbeat detectable from around 6 weeks gestational age

Question 35

how are the lungs formed?

Answer 35

endodermal structure

arise from the lung bud, just adjacent to the foregut

in the fourth week of development

lung bud splits into two at the end of the fourth week, and progressively branches through development

Question 36

how do the gonads form?

Answer 36

mesodermal

initially bipotential ( not committed to testes or ovaries)
structures known as gonadal/genital ridges

XY embryos:
presence of SRY gene on y chromosome directs gonadal cells to become sertoli cells, triggering testis development, leydig cell formation and testosterone production

XX embryos:
absence of SRY leads to gonadal cells adopting a granulosa cell fate and ovary development
requires reinforcement by FOXL2