Human embryonic development

Question 1

Describe what happens in first week of human embryonic development (fertilisation and pre-implantation).

Answer 1

Day 0: Oocyte is released from the ovary in the female reproductive tract and passes down the fallopian tubes.

Day 1-4:When fertilisation occurs -> sperm penetrates ovum, and first cleavage stage occurs in the oviduct.
Early embryo has egg cell uncompacted morula.

Day 5: Formation of blastocyst -> which develops when there’s cavity inside embryo. Group of cells located on one side (inner cell mass), a group of cells around the outside (trophoblast or trophoectoderm).

Day 6-7: Embryo hatches or emerges from zona pelucida (glycoprotsin coat) that surrounds embryo and then impants into the wall of uterus into the endometrium.

Question 2

What happens in the weeks 1-3 (cleavage, implantation and gastrulation) stage?

Answer 2

Day 1 (Fertilisation): Male and female pronucleus meet.

Day 2 (Cleavage): Rapid cell division generates tight ball of cells during compaction.

Day 3 (Compaction: morula): Embryo as morula (solid ball of cells)

Day 4-5 (Blastocyst formation): Cavity appears in embryo (called blastocyst). Blastocyst has outer trophoblast and inner cell mass. Inner cell mass gives rise to entire embryo and embryonic stem cells. Trophoblast gives rise to embryonic portion of placenta.

Day 6 (Hatching): Hatching from zona pellucida from coat that surrounds early embryo.

Day 7 (Implantation): Implants into wall of uterus, into uterine epithelium shown here.
Then:
- Inner cell mass resolves into two cell groups; Upper epiblast, lower hypoblast, and trophoblast. Embryo forms from inner cell mass, trophoblast forms embryonic component of placenta.
- Hypoblast forms primitive yolk sac.

Day 8-12 (Bilaminar disc): Two layers; epiblast and hypoblast.

Day 12 (Gastrulation): Formation of 3 germ layers:

- Epiblast cell migrate through primitive streak, Displace hypoblast to form endoderm. 
- Second wave of cells migrate through primitive streak of epiblast to form mesoderm. 

Day 18 (Mesoderm spreading): Mesoderm spreads out around embryo and contributes to chorion. 
Embryo has three tri-layers: 
	- Epiblast -> ectoderm 
	- Mesoderm 
	- Endoderm

Question 3

What specific body parts do the three germ layers form?

Answer 3

Ectoderm: brain, nervous system, epidermis

Mesoderm: muscles, bones, heart and blood vessels urogenital system

Endoderm: lining of gut, liver, pancreas

Question 4

What is a pregnancy test? What hormone does the test rely on? How is it detected?

Answer 4

A biochemical test to determine if a woman is pregnant.

Modern tests rely upon the hormone, human chorionic gonadotrophin (hCG) secreted by placenta after embryo implantation and detectable in maternal blood and urine.

hCG cannot be detected until after implantation (day 7-8).

Question 5

What happens in ectopic pregnancy:?

Answer 5

Embryo implants outside uterus. Rather than implanting into accommodating wall of uterus, it will implants in wall of fallopian tubes -> this causes bleeding and tubal miscarriage.

Also, early embryo can dislodge from fallopian tube. And be embedded somewhere else (e.g. gastrointestinal tract) -> failed pregnancy.

Question 6

What is a hydatidiform mole?

Answer 6

Inner cells mass resolves into bilaminar disc, upper epiblast, and lower hypoblast.
Epiblast gives rise to embryo proper, but if that fails due to congenital malformation -> trophoblast can proliferate alone and not embryo.

Question 7

Why does a pregnancy test show normal results despite of hydatidiform mole?

Answer 7

The trophoblast cells will secrete human chorionic gonadotropin (hCG), as in a normal pregnancy, and may appear maternally and by pregnancy test to be “normal”. Prenatal diagnosis by ultrasound analysis demonstrates the absence of a embryo.

Question 8

What are the symptoms of Hydatiform mole?

Answer 8

Abnormal growth, vaginal bleeding, 80% are benign and are removed.

Question 9

What is neurulation and neural tube?

Answer 9

Neurulation: formation of the neural tube (future brain and spinal cord)
Neural tube is specialised ectoderm on dorsal embryo surface

Question 10

How does the groove of neural tube fold?

Answer 10

Induced by growth factors, or inductive signals from underlying notochord

Question 11

What is the general process of neurulation?

Answer 11

1) . Groove invaginates -> tube folds, neural folds on either side.
2) . Notochord releases inductive signals -> induces invagination.
3) . Cells of neural crest border (neural crest cells) pinch off and migrate away.

Question 12

When do neural tube defects occur:

Answer 12

Occurs early in pregnancy (first trimester).

Question 13

What are some examples of neural tube defects?

Answer 13

Anencephaly: the cephalic part of neural tube fails to close, leading to absence of a major portion of the brain (babies can be born, but are deaf, blind, unconscious).

Spina bifida: incomplete closure of posterior neural tube: varies in severity : vertebrae remain open, part of spinal cord is exposed : causes neural disability : risk greatly reduced by folic acid supplementation before conception : familial or sporadic.

Sporadic = The sporadic form of the disease can affect anyone and is dependent on genetic changes acquired during the lifetime of the affected individual.

Question 14

What are neural crest cells?

Answer 14

A population of cells derived from junction of neural plate and epidermis.

Question 15

What is the process in which neural crest cells migrate?

Answer 15

• Neural plate folds and closes to form neural tube.
  
  • Cells at this border junction will bud off and migrate away because they’re going from epithelian to mesenchyme transition.

Question 16

What do neural cress cells contribute to?

Answer 16

Melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral & enteric neurons.

Question 17

What are some derivatives of neural crest cells?

Answer 17

Neural crest cells give rise to craniofacial region (cartilage and bone), odontoblasts (dentine of teeth), melanocytes (pigment cells), parts of the heart, branchial arch derivatives (throat), parts of peripheral nervous system.

Check slide to see what cranial…. Neural crest cells give rise to.

Question 18

What is the first organ to function in an embryo?

Answer 18

Heart

Question 19

Briefly describe the formation of the heart during organogenesis (weeks 3-4)?

Answer 19

• Heart tubes fuse in midline to form early heart tube
  
  • Heart fold upon itself to form 4 chambers of heart.
  • Heart begins to beat at day 22-23.

Question 20

What are two broad types of abnormalities in embryonic development?

Answer 20

1. Genetic (inherited or de novo (from new; weren’t present in mother or father)
2. environmental (effects of teratogens - toxins, these modify development.)

Question 21

What are the three broad types of genetic defects that cause embryonic and postnatal abnormalities

Answer 21

1. Single gene defects (about 4000 known diseases)
2. Alterations in larger chromosomal segments (Multiple genes)
3. Chromosomal defects (large scale; loss or gain of DNA)

Question 22

Is single gene disorder (e.g. Duchenne muscular dystrophy) X-linked dominant or recessive? What is it caused by? What are the symptoms?

Answer 22

• X-linked recessive.
  
  • Caused by a loss of function mutation of dystrophin gene, that encodes key structural component of muscle tissue.
  • Results in muscle degeneration, difficulty walking ,breathing, death

Question 23

What is Dystrophin?

Answer 23

Dystrophin is a rod-shaped protein that connects cytoskeleton of muscle fibre cell to surrounding ECM

Question 24

What type of test is used to confirm if child has Duchenne muscular dystrophy or not?

Answer 24

Prenatal tests can tell whether their unborn child has the most common mutations. (only works if mutation known in family).

Question 25

What mutations does Prader-Willi and Angelman’s occur due to?

Answer 25

Occurs due to o loss of function of several imprinted genes on ch15q11-13; Paternal loss = Prader-Will ; maternal loss = Angelman’s.

Look at slides for an awesome example.

Question 26

What are the symptoms of Angelman and Pradar-Willi syndrome?

Answer 26

Prader-Willi: affects several body parts: weakened muscle, poor growth delayed development, learning impairment; obesity; distinct angular face; mostly infertile. severe developmental delay and learning disabilities • absence or near absence of speech • inability to coordinate voluntary movements (ataxia) • happy disposition and unprovoked episodes of laughter and smiling.

Angelman’s: epilepsy, tremors, constant smiling, learning problems. include weak muscles, • constant hunger, which often leads to obesity and type 2 diabetes. • Mild to moderate intellectual impairment and behavioural problems • a narrow forehead, small hands and feet, short height, light skin and hair.

Question 27

What is a chromosomal disorder?

Answer 27

Genes unaltered but a chromosome is duplicated or deleted.

Question 28

What is a down syndrome? What is its mechanism?

Answer 28

• Down syndrome is due to trisomy 21.
  
  • The main genes responsible for Down Syndrome cluster at around 21a or short or long arm of chromosome 21.
  • Instead of chromosome 21 going to one pole and one copy going to other pole, both copies go to one pole. So when they divide again by meiosis two, you end up with three copies of chromosome 21. Some cells and only one copy. At least one copy tend not to be viable, but the three copies version, then these are gametes. When those meet copies or gametes from other sex, this results in trisomy or three copies, resulting in embryo and the newborn.

Question 29

What are the symptoms of down syndrome?

Answer 29

Features: mental retardation, particular set of facial features (small chin, rounded face) increased incidence of heart disorders, hearing loss.

Question 30

What is a distinguishing feature in humans?

Answer 30

Encephalisation (brain development).

Question 31

What is the difference in cerebral cortex between humans and chimpanzees?

Answer 31

Cerebral cortex is much more folded, harbouring more neurons and connections between regions. Highly developed: that part of cortex involved in sensory reception, conscious thought, language, abstraction, problem solving

Question 32

Why does human brain growth out-strips that of other apes?

Answer 32

• Neocortex of human brain maintains its foetal growth rate.
  
  • Human brain is highly plastic, constantly changing, re-modelling.
  • There’s high levels of gene transcription.

Question 33

What are HARs (human accelerated regions)?

Answer 33

Rapidly evolving DNA regulatory elements, often located near brain-expressed genes.

Question 34

What is an example of HARs?

Answer 34

e.g., HARE5, regulates Frizzled8, a receptor involved in neuron growth.

Question 35

Compare the cortex size of mouse expressing human and chimpanzee HARE5?

Answer 35

Transgenic mice and they are expressing the chimp or human HARE5 regulatory region that is driving LacZ reporter expression.

Question 36

So the regulatory region, this HARE5 five regulatory region which regulates frizzled8. This regulatory region is driving an expression of LacZ, which stains blue, such reporting the activity of the Hare five regulator region. Compare the staining intensity between humans and chimpanzee HARE5 in mouse embryo.

Answer 36

So, embryonic mouse embryos over embryonic day 10.5, chimp HARE5 regulatory region shows some activity in the mouse. But in human, it has much stronger activity and it shows a greater staining intensity. And so this suggests or indicates that the human HARE5 regulatory region is a much more active and a stronger regulatory region than the chimp tested in this mouse model.

Question 37

In some cases, unique human traits have evolved through DNA loss
McLean et al. (2011) identified 510 genomic regions present in chimps & other but mammals but deleted in humans (almost all non-coding). Give an example of a gene that has been lost in human but has led to increased human brain growth.

Answer 37

Loss of brain enhancer of the growth suppressor, GADD45G. Loss of GADD45G expression may be linked to increased brain growth in humans.

Question 38

Design an experiment that shows loss of genes in humans that led to increased human brain growth.

Answer 38

1) . So researchers took chimp GADD45G forebrain enhancer linked that to LacZ reporter and then put that into mice (you can see blue staining).
2) . Report shows expression of chimp GADD45 enhancer was very strong compared to mouse enhancer.
3) . When they put the human GADD45G forebrain enhancer (this is a growth suppressor). When they put the LacZ reporter mouse, there was no real activity.

Thus, there has been loss of growth suppressor allowing enhanced growth of human brain.

Question 39

What is neoteny?

Answer 39

Neoteny: retention of juvenile traits in adults : developmental rate of one tissue/organ is slower than other tissues.

Question 40

Do humans or chimpanzees show evidence of neoteny?

Answer 40

Humans show evidence of neoteny ( e.g., little body hair, small jaws, lengthened period of youth ; growth and development of the skull).

Question 41

Compare brain development of humans and chimpanzees in terms of measures of skull development.

Answer 41

Chimps shows a larger brain development pattern (again through measures of skull development) than humans.

Question 42

Where does gene transcriptional neoteny occur? Do embryonic expressed gene express longer at postnatal stages in humans or chimps?

Answer 42

Gene transcriptional neoteny occurs in frontal cortex of brain (embryonic expressed genes still expressed longer at postnatal stages in human vs chimp).