Mechanisms Of Disease During Embryogenesis

Question 1

Human development
State the periods of the human development and features of them?

Answer 1

• Two main periods:
• Embryonic period: Up to the end of week 8, Most of the organogenesis (establishment of organs and tissues) occurs in these first 8 weeks.
• Fetal period: The remaining time in utero (unborn baby from after 8 weeks till birth), Involves growth and modeling (of initial organs)

Question 2

What can occur if defects during embryogenesis happen?

Answer 2

• Congenital malformations
• The earlier the defects occur in processes, the more serious the condition is

Question 3

Mechanisms of development
State in order the mechanisms of development that occur from egg to adult?

Answer 3

• From egg:
  1. fertilisation
  2. cleavage
  3. gastrulation
  4. neurulation and somitogenesis
  5. organogenesis
• To adult

Question 4

Briefly describe fertilisation?

Answer 4

1. Fertilized zygote is formed here after the female and male pronuclei have joined together in the ampulla of the uterine tube.
2. After this the zygote will pass to the uterus and it will undergo a number of cleavage steps
3. Before the development of the embryo proper, the conceptus must first implant, then generate the “germ” disc (epiblast and hypoblast of blastocyst). This takes ~10 days.

Question 5

Describe the cleavage step?

Answer 5

Division of zygote (with haploid pronuclei) - 2-cell zygote - 4-cell zygote -> Morula (12-16 cells at day 3)

Question 6

Describe the cleavage step (PART 2)

Answer 6

• Morula undergoes compaction (first major reorganisation)
• Forms inner cell mass and blastocoele (fluid filled cavity), where the zona layer dissolves
• Day 6/7 also forms a trophoblast cell layer
• At days 4/5, where 32-64 cells are formed, a blastocyst is made which is ready to implant

Question 7

Describe the cleavage step (PART 3)

Answer 7

• Day 9: Full implantation occurs
• Here inner cell mass forms the bilaminar germ disc which is the epiblast and hypoblast cells of the blastocyst
• Another cavity also forms known as the amniotic cavity

Question 8

Describe the gastrulation phase?

Answer 8

• Gastrulation = Formation of a flat structure of 3 layers (ectoderm, mesoderm, endoderm) from the germ disc
• Gastrulation process: from 2 layers to 3.
• Hypoblast (primitive endoderm) is displaced by involuting cells (epiblast cells move down the primitive groove to displace) that become definitive endoderm and mesoderm
• The epiblast cells forms the ectoderm layer
• So layers from top to bottom are ectoderm, mesoderm and endoderm

Question 9

Neuralation (and somitogenesis)
Describe how neuralation establishes the CNS?

Answer 9

1. At 15 days, the primitive streak (marking start of gastrulation starts moving to the other side of the embryo?)
   - The primitive streak is a transient structure whose formation, on day 15 of human development, marks the start of gastrulation, the process in which the inner cell mass is converted into the trilaminar embryonic disc, which is comprised of the three germ layers (ectoderm, mesoderm and endoderm).
2. At 18 days, it reaches near the other end (prochordal plate) where it starts to regress.
   - As it moves down it leads a rod of cells along axis K known as the notochordal process (source of neural inducers)

Question 10

Neuralation (and somitogenesis)
Describe how neuralation establishes the CNS? (PART 2)

Answer 10

3. Notochord cells are found below the ectoderm. Here the cells secrete extracellular molecules (via signalling to overlying ecotderm) which convert ectoderm cells into neural tissue. This establishes the neural plate (primordial of the CNS)
4. From 19-20/21 days, as PS regresses further, a neural plate forms on top of the notochord cells

Question 11

State how neural tube closure occurs?

Answer 11

1. At day 20, Neural folds start at edge of hindbrain and spinal cord.
2. Here the folds meet and fuse together to create the neural tube. a. Neural folds also rise out of the plane of the disk?
3. The folds progess anoterioly and posterioly until the whole neural plate becomes folded into a tube at day 22.
   - a. Here the surface ectoderm will be covering the tube
   - b. Mesoderm cells reorganise to form tissue blocks (precursors of bones + muscles)

Question 12

What other processes are neuralation associated with?

Answer 12

• Neurulation is associated with other form-shaping (morphogenetic) processes, particularly gut
• Formation and body folding (“silk purse” model)
• Occurs via the mesoderm and endoderm

Question 13

What occurs in folding?

Answer 13

1. Starts with an open formation cord round margins?
2. Folding occurs to form purse ‘neck’ (week 4-5)
   a. Here septum and heart move from margin to centre.
   b. Yolk sac, allantois and stalk make umbilical cord
   c. Prochordal and cloacal plates delimit gut tube
   d. Major results of folding are umbilical cord and gut

Side info from Shariq’s notes: Just clocked somitogenesis is more the neural plate and tissue blocks, but it wasn’t specifically referred to in the lecture

Question 14

What occurs in organogenesis?

Answer 14

• Differentiation of somitic derivatives: bones, muscles, tendons
• Development of sensory organs: ears, eyes, olfactory pits
• Limb formation: forelimbs first, hindlimbs next, establishment of pattern in the limbs: proximodistal, anterior-posterior, dorsal-ventral
• Formation of facial structures: jaws, nose, tongue, palate
• Formation of genital structures

Question 15

What desirable characteristics must model organisms have so we can understand how embryos develop and state an example?

Answer 15

• Relevance/representative
• Accessibility/availiability
• Experimental manipulation
• Genetics
• Cost/space

Question 16

Causes of development (congenital diseases
What is a single gene mutation?

Answer 16

Refers to the cases when mutation in one particular gene will be enough to display a characteristic defect.

Question 17

What is a chromosomal anomalie?

Answer 17

• In some cases, rather than single mutations, whole chromosomal rearrangements are responsible for a disease.
• The most obvious examples are chromosomal trisomies, such as trisomy of chromosome 21, leading to Down syndrome.

Question 18

What is a polygeneic disorder?

Answer 18

Refers to cases where it is not just one gene affected, but several different genes simultaneously affected, that causes the disease.

Question 19

What are environmental factors?

Answer 19

• Refers to the deleterious influence of the environment on a particular process.
• These can be very diverse: diet, infection, toxic compounds.

Question 20

What is multifactorial aetiology disorder?

Answer 20

• Combination of intrinsic (genetic) and extrinsic (environmental) factors that influence embryonic development and are at the basis of a congenital disease
• Most cases occur due to this

Question 21

Summary of key points in the lecture

Answer 21

• Human embryonic development is a very complex process, controlled by networks of genes acting together.
• Defects in gene function during this process will result in defective embryonic development.
• Some genes are needed at several different stages of embryonic development, or in several organs. Alterations in the function of such genes will result in complex phenotypes in a variety of tissues. These are called syndromic diseases.
  • Embryonic development can also be perturbed by environmental insults, maternal diet deficiencies or infections during pregnancies.
  • Often, it is a combination of genetic and environmental causes what results in congenital disease.
  • Identifying the relative contribution of these factors is a challenging and often very difficult process.

Question 22

Summary of key points in the lecture

Answer 22

• Embryonic development can also be perturbed by environmental insults, maternal diet deficiencies or infections during pregnancies.
• Often, it is a combination of genetic and environmental causes what results in congenital disease.
• Identifying the relative contribution of these factors is a challenging and often very difficult process.