Mechanisms of disease during embryogenesis

Question 1

What are the two main periods in human development?

Answer 1

Embryonic period:

• Up to the end of week 8
• Most of the organogenesis occurs in these first 8 weeks

Fetal period:

• The remaining time in utero
• Involves growth and modelling
• and refinement of those initially specified organs and tissues

Defects during embryogenesis results in congenital malformations. Embryo doesn’t develop properly and shows when a baby is born.

Question 2

What steps does the organism go through during emrbyogenesis?

Answer 2

From egg:

• Fertilisation
• Cleavage
• gastrulation
• Neurulation and somitogenesis
• Organogenesis

To keep growing until it gives rise to adult form

Question 3

Step 1, fetilisation

Where does fertilisation occur? What happens during this time?

Answer 3

In the fallopian duct, first stage of development occurs as the embryo travels to uterus. Takes 10 days in human cycle.

Fertilised zygote undergoes series of cleavages to give rise to morula.

First reorganisation of these cells gives blastocyst.

Question 4

Stage 2, Cleavage.

What happens during the cleavage stage?

Answer 4

Fertilised zygote divided into 2 cells, then 4, 8, 16.

Once it gets to 8-16 cell stage it is a morula.

Now ready to undergo reorganisation - process called compaction.

Question 5

Cleavage

Describe the arrangement of cells in compaction

Answer 5

• Cells in embryo sort themselves to be exterior and others interior (within embryo)
• Cells outside have strong cell-cell contact with neighbouring cells + have one of their surfaces exposed to the extracellular environment - gives polarity
• Cells have apical surface (not in contact with any cell) and basolateral surface (in contact with surrounding cells)
• Cells inside embryo are apolar, all sites in contact with other cells
• Cells outside give rise to trophectoderm, cells inside - inner cell mass

Question 6

Cleavage

How is the blastocoele formed?

What does the inner cell mass give rise to?

Answer 6

• Cells outside pump fluid into embryo, forms fluid filled cavity, blastocoele
• Blastocoele pushes inner cell mass to one side, asymmetry to embryo
• Embryo is now a blastocyst, stage with 32-34 cells
• Blastocyst has reached the uterus and is ready to implant in uterine wall
• Inner cell mass gives rise to 2 cells, cells lining at edge of inner cell mass in the blastocele, hypoblast
• And epiblast, remain on opposite and not in contact with blastocele - gives rise rise to amniotic cavity

Question 7

Gastrulation, second main reorganisation

Describe the process of gastrulation

Answer 7

• Leads to formation of 3 layers of cells from the germ disc (bilayer)
• Groove forms on the epiblast at one end of bilaminar germ disc - primitive groove
• Cells from epiblast ingress through groove and spread beneath epiblast
• displace hypoblast and form endoderm and mesoderm beneath epiblast layer, giving rise to ectoderm

Question 8

Neurulation, first steps

How is the notochordal process formed?

Answer 8

• Gastrulation and ingress along the primitive groove of cells gives rise to the endoderm and mesoderm,
• primitive streak extends along epiblast, gastrulation occurs
• primitive streak reaches other end, starts regressing and lays down rod like structure under ectoderm - notochordal process

Question 9

Neurlation

What does the notochord secrete? What do we end up with?

Answer 9

• Notochord is a rod of cells that secrete number of extracellular molecules, that instructures ectoderm ontop of it to become neural tissue
• primitive streak progresses, notochord extended posteriorly.
• As it extends it instructs overlying ectoderm to become neural plate

Question 10

Neurulation

What happens after the neural plate forms?

Answer 10

• Neural plate folds to give rise to the neural tube and becomes buried inside the embryo as it folds
• Edges come together and detach from surrounding ectoderm, giving rise to neural tube under the ectoderm
• closure of neural tube starts at edge between hind brain and spinal cord, progresses anteriorly and posteriorly
• same time mesoderm cells become segmented into tissue blocks - tissue block somites
• Somites are precursors of bones, muscles and tendons

Question 11

Folding

What is the cloth purse model?

Answer 11

• Septum and heart move from margin to centre of embryo, beneath ectoderm. Whole ectoderm folds around it.
• Folding leads to formation of Yolk sac, allantois and stalk make umbilical cord - and cut
• Prochordal and cloacal plates delimit gut tube

Question 12

Organogenesis

What happens during organogenesis?

Answer 12

Towards end of first 8 weeks

See differentiation of somitic derivitates

• Gives rise to bones, muscles and tendons

Development of sensory organs

• Gives rise to ears, eyes, olfactory pits

Limb formation

• Forelimbs first, hindlimbs next
• Estabilishment of pattern in the limbs: proximodistal (arms, hand), anterior-posterior (digits in hands), dorsal ventral (Differences in front and back of hand)

Formation of face structures

• Jaws, nose, tongue, palate

Formation of genital structures

Question 13

What does defects during embryogenesis result in?

Answer 13

Defects in first two weeks lead to spontaneous abortion.

3-9 weeks causes major congenital malformations, affecting whole systems and organs.

Defects later one may be functional deficiencies or minor anomalies.

Question 14

What are some desirable characteristics of a model organism?

Answer 14

Relevance/representative , a model organism that we can learn things that help us understand human embryonic development

Accessibility/availability to work with them easily in laboratory setup

Experimental manipulation on their embryos to learn from the manipulations how development takes place

Genetics, need good understanding of their genetics and their genome is fully sequenced. And that we can manipulate the genome to understand the gene functions.

Cost/space to maintain such model organism