Mechanisms of Disease during Embryogenesis Flashcards

1
Q

Describe the embryonic period

A

Up to the end of week 8. Most of the organogenesis, tissue and body plan occurs in these first 8 weeks.

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2
Q

Describe the fetal period

A

The remaining time in utero after the embryonic period. It involves growth and modelling. Also refinement of previous develpoment of organs and tissues.

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3
Q

Defects during embryogenesis result in…

A

congenital malformations

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4
Q

What are the stages of development?

A

From egg - fertilisation, cleavage, gastrulation, neurulation and somitogenesis, organogenesis - to adult

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5
Q

Describe a newly fertilised egg

A

The zygote consists of two pronuclei, polar bodies which are the product of meiosis that generate the oocyte and the hard, outer zona pellucida layer.

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6
Q

Explain fertilisation briefly

A

It occurs in fallopian duct. Takes around 10 days for fertilised egg to make its way to uterus. The fertilised egg undergoes a series of cleavages before becoming a morula and then reorganising to become a blastocyst.

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7
Q

What happens when the zygote undergoes cleavage?

A

First, it divides and becomes the 2-cell zygote then 4-cell zygote. Once it reaches a 12-16 cell stage, it becomes a morula. It is now ready to undergo first main reorganisation via compaction to become a blastocyst. The cells on the outside gives rise to the trophectoderm and cells on inside give rise to inner cell mass. The outer cells pump liquid into zygote to form a blastocoele. This now leaves a blastocyst consisting of 32-64 cells at days 4/5. At days 6/7, it is now ready to implant into uterus. At day 9, it has fully implanted into the uterine wall. A bilayer germ disk forms consisting of epiblast and hypoblast cells.

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8
Q

What happens during gastrulation?

A

The bilaminar embryonic disc undergoes reorganisation to form a trilaminar disc.
At the epiblast cells, at one end of the germ disk, the primitive groove is formed and epiblast cells migrate inwards towards the primitive streak, detach from the epiblast and slip beneath it into the interior of the embryo. The first cells to invaginate the primitive groove invade the hypoblast and displace its cells. These cells are eventually replaced fully by a new cell layer which is called the endoderm.
The remaining cells of the epiblast are now referred to as the ectoderm, and forms the most exterior, distal layer. Some of the invaginated epiblast cells remain in the space between the ectoderm and the endoderm to form a germ layer known as the mesoderm.

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9
Q

What happens during neurulation?

A

Primitive streak extend alongs epiblast and as this happens gastrulation occurs. However, once the streak reaches the other end, it regresses and lays down a rod-like structure, that is just under the ectoderm, called the notochord. This is a group of cells that secrete extracellular molecules that instruct the ectoderm to become neural tissue. This forms the neural plate (just on top of the notochord) which continues to extend as the primitive streak regresses.
The neural plate gives rise to the neural tube. This takes place through neural folds rising out of the plane of the disk. They meet and fuse to create the neural tube. The surface ectoderm covers the tubes. This is the start of the CNS.
The neural tube does not fuse and become one tube all at once. It starts at the middle (between the hindbrain and the spinal cord) and works it’s way out posteriorly and anteriorly like a zip.

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10
Q

What happens during somitogenesis?

A

As neurulation is taking place and the ectoderm is reorganising, the mesoderm cells are also undergoing reorganisation. They are located just under the ectoderm and the mesodermal cells start to become segmented in tissue blocks - called somites. These are precursors of bones, muscles and tendons etc.

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11
Q

Neurulation is related to other form-shaping (morphogenetic) processes, particularly gut formation and body folding (‘silk purse’ model). What does this mean?

A

Alongside neurulation and somitogenesis, other processes are working alongside it too.
The embryo till now is currently flat but the mesoderm and endoderm give rise to all our internal organs so they need to be enclosed in the developing embryo. It does this by folding over itself.

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12
Q

What happens during ‘folding’?

A

According to the ‘cloth purse model’, it’s like the embryo is an open bag with a cord round the margins. The cords are brought close together to fold and form the ‘purse neck.’
The embryo is changing shape from a flat trilaminar disk to a cylinder. It is the result of differing rates of growth of the embryonic structures.
The septum and heart move from margin to centre. The yolk sac, allantois and stalk make umbilical cord. Prochordal and cloacal plates delimit gut tube.

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13
Q

What happens during organogenesis?

A

At the end of the first 8 weeks:

  • 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 (e.g. your hand at the end of your arm), anterior-posterior (e.g. the order of your digits), dorsal-ventral (e.g. difference in appearance in front and back of your hand)
  • Formation of face structure = jaws, nose, tongue, palate
  • Formation of genital structures
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14
Q

What happens if there are defects in the first two weeks of pregnancy?

A

Most likely the embryo will die

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15
Q

What happens if there are defects in weeks 3-8/9 of pregnancy?

A

Most likely have major congenital abnormalities.

Affects whole organs and usually several organs at the same time.

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16
Q

What happens if there are defects in weeks 9-38 of pregnancy?

A

There are functional defects and minor anomalies - not as severe malformations as defects earlier in pregnancy but still deleterious for life.

17
Q

What are the desirable characteristics of a model organism?

A
  • Relevance/representative (help us to understand human embryonic development)
  • Acessibility/availability (easy to work with in a lab setup)
  • Experimental manipulation (need to be able to change embryos so we can learn from them)
  • Genetics (need good understanding, ideally fully sequenced genome and that we can manipulate genes to understand gene function)
  • Cost/space
18
Q

Why are zebrafish a popular model organism?

A

Their genome has been sequenced to a high standard.
They are very easy to maintain and look after large numbers in a lab setting.
They have transparent embryos so very easy to see as each embryo develops.
The genome is extremely similar - over 70%. You can work thru the genome and see the effects of mutations and their consequences. You can also use them for drug research to see if it helps symptoms etc.

19
Q

Single gene mutations

A

refers to the cases when mutation in one particular gene will be enough to display a characteristic defect.
autosomal = not sex-specific - recessive/dominant
X-linked = sex-specific - recessive common in males as only one X, dominant more common in females

20
Q

Chromosomal anomalies

A

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. This is when you have three chromosomes present instead of two.

21
Q

Polygenic disorders

A

refers to cases where it is not just one gene affected, but several different genes simultaneously affected, what causes the disease. Doesn’t involve the environment.

22
Q

Environmental factors

A

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

23
Q

Multifactorial inheritance disorders

A

describes a trait whose manifestations are determined by two or more genes, accompanied by environmental factors.