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Mammal development Flashcards

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1
Q

Why is it important to study mammalian development?

A

To understand the process from a fertilised egg to a functional organism and its regulation

Understanding mammalian development can inform us about congenital abnormalities and potential medical treatments.

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2
Q

What are the key differences in mammalian development compared to other vertebrates?

A

Mammalian embryos implant into the uterus and gain nourishment from the maternal environment, unlike other vertebrates

This includes evolutionary adaptations that shape developmental mechanisms.

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3
Q

What is Evo-Devo?

A

The comparison of developmental processes across different species

This field helps to understand evolutionary adaptations in developmental biology.

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4
Q

What percentage of births in the UK are estimated to have congenital abnormalities?

A

1 in 47 births

Congenital abnormalities can range from minor issues to life-threatening conditions.

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5
Q

What are some examples of congenital abnormalities?

A
  • Polydactyly
  • Spina bifida

These conditions can arise from genetic mutations or environmental factors.

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6
Q

What is the main question of mammalian development?

A

How the organised structure of the body plan is established from a single egg cell

This includes understanding the coordination of tissues and organs.

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7
Q

What dichotomous concepts has developmental biology wrestled with?

A
  • Epigenesis vs. Preformationism
  • Vitalism vs. Materialism
  • Mosaic development vs. Regulative development

These concepts help compare developmental regulation mechanisms.

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8
Q

What is the main model organism for mammalian developmental biology?

A

Mouse

Mice are used due to their evolutionary similarity to humans and ease of experimentation.

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9
Q

What is the significance of IVF in mammalian development?

A

It allows for the reproduction of fertilisation and early embryo development in the laboratory

IVF was pioneered in 1969, leading to the first successful human birth.

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10
Q

What happens during the cleavage events after fertilisation?

A

The zygote undergoes cell divisions to form blastomeres and eventually a morula

At the 8-cell stage, compaction occurs, leading to the morula stage.

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11
Q

What is the first cell fate decision in early mammalian development?

A

The formation of Trophectoderm (TE) and Inner Cell Mass (ICM)

This decision occurs during the morula stage.

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12
Q

What is a blastocyst?

A

An embryo at the stage where it has formed a blastocoel and consists of TE and ICM

The blastocyst stage is crucial for implantation.

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13
Q

What is the role of the Hippo signalling pathway in early mammalian development?

A

It helps determine cell fate based on cell position and polarity

It does not use diffusible ligands but relies on cell contacts.

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14
Q

What transcription factor is expressed in TE cells?

A

Cdx2

Cdx2 is a marker for Trophectoderm cells.

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15
Q

What transcription factor is expressed in ICM cells?

A

Oct4

Oct4 is crucial for the identity of Inner Cell Mass cells.

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16
Q

What is a negative feedback loop in the context of cell fate decisions?

A

A configuration where two transcription factors downregulate each other’s expression

This mechanism ensures cells differentiate into one of two types.

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17
Q

What are the two transcription factors involved in the second fate decision of the ICM?

A
  • Nanog
  • Gata6

These factors are initially co-expressed before cells segregate into Epiblast and Primitive Endoderm.

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18
Q

How is the right proportion of cell lineages ensured in embryonic development?

A
  • Sequential binary cell fate decisions
  • Signalling feedback systems
  • Spatiotemporal regulation

These mechanisms help coordinate cell fate decisions effectively.

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19
Q

What are the two transcription factors initially co-expressed in the early embryo?

A

Nanog and Gata6

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20
Q

What patterning do PrE cells exhibit during their initial differentiation?

A

Salt-and-pepper patterning

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21
Q

What is the role of the FGF4 ligand in cell fate decisions?

A

It signals neighboring cells to downregulate Nanog and upregulate Gata6

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22
Q

What experimental methods confirm the role of FGF signaling in maintaining cell proportions?

A

FGF signaling inhibition or activation experiments

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23
Q

What are the two types of development in early embryos?

A
  • Regulative development
  • Mosaic development
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24
Q

What did early experiments on mouse 4-cell stage embryos show?

A

They could be divided and occasionally give rise to normal blastocysts

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25
What do half and double mouse embryos demonstrate about cell fate decisions?
They maintain the correct proportions of cell types
26
What is the gold-standard test of pluripotency in developmental biology?
A cell contributing to all lineages of an embryo including germ cells
27
What is the significance of tetraploid (4n) embryos in developmental studies?
They can form complete embryos from individual blastocysts
28
What technique uses biopsied blastomeres from human embryos?
Preimplantation genetic diagnosis (PGD)
29
What defines a cell's 'state' in developmental biology?
A particular transcriptional profile at a point in time
30
What is cellular potency?
The potential of a cell to differentiate into various cell types
31
Who proposed the epigenetic landscape model?
Conrad H. Waddington
32
What does the epigenetic landscape represent in developmental biology?
The progression of cells through decision points leading to differentiation
33
What does the term 'stochasticity' imply in development?
There is variability in cell fate decisions among similar cells
34
What happens to a cell's potential as it differentiates?
It becomes progressively restricted
35
How do adult stem cells differ from embryonic stem cells?
Adult stem cells are multipotent; embryonic stem cells are pluripotent
36
What are the two main forms of stem cells?
* Adult stem cells * Embryonic stem cells
37
What environmental condition allows mouse ESCs to maintain pluripotency in culture?
Growth in a BMP-rich medium
38
What are Yamanaka factors?
Oct4, Sox2, Klf4, and Myc
39
What are induced Pluripotent Stem Cells (iPSCs)?
Somatic cells reverted to a pluripotent state using Yamanaka factors
40
What is the significance of the Waddington's epigenetic landscape in understanding cellular differentiation?
It illustrates how cells reach discrete states during development
41
What is the process by which differentiated cells can revert to an earlier state of pluripotency?
Induced pluripotency ## Footnote This process is facilitated by introducing specific genes, known as Yamanaka factors.
42
What are the four Yamanaka factors used to induce pluripotency?
* Oct4 * Sox2 * Klf4 * Myc ## Footnote These factors are commonly referred to as OSKM factors.
43
What are induced Pluripotent Stem Cells also known as?
iPSCs ## Footnote iPSCs are derived from differentiated cells that have been reprogrammed.
44
What are some applications of pluripotent stem cells?
* Revealing regulation of cell fate decisions * Revealing self-organisation properties * Therapeutic applications ## Footnote iPSCs have potential for drug development and cell therapy.
45
What are embryo-like models?
Multicellular entities that display similarities to the embryo ## Footnote They are generated from pluripotent stem cells and can be created in vitro.
46
What are the advantages of using embryo-like models in research?
* Highly scalable * Experimentally tractable * Can be derived from patient cells * Enhance understanding of embryogenesis ## Footnote They provide insights into cell fate decisions and pattern formation.
47
What is the difference between integrated and non-integrated embryo-like models?
* Integrated models: contain both embryonic and extraembryonic tissues * Non-integrated models: model specific aspects of embryo development ## Footnote Examples include blastoids (integrated) and micropatterns (non-integrated).
48
What is gastrulation?
A morphological process where the embryo defines spatial axes and generates germ layers ## Footnote It involves the formation of endoderm, mesoderm, and ectoderm.
49
Which axes does the embryo define during gastrulation?
* Anterior-posterior * Dorsal-ventral * Medio-lateral * Left-right ## Footnote These axes are critical for proper body plan organization.
50
What is the primitive streak?
A structure that forms at the posterior region of the embryo during gastrulation ## Footnote It is where epiblast cells migrate to differentiate into mesoderm and endoderm.
51
What role do Neuromesodermal Progenitors (NMPs) play in embryonic development?
They contribute to both neural and mesodermal lineages ## Footnote NMPs reside in the posterior part of the embryo.
52
What is the significance of the left-right axis in the mammalian embryo?
It is crucial for the correct folding of the heart tube and organ location ## Footnote The node specifies this axis through cilia movement.
53
What is the phylotypic stage?
A shared set of stages in embryonic development across different species ## Footnote It shows high similarity before diverging into species-specific development.
54
What are Hox genes?
A set of genes that determine the positional identity along the anterior-posterior axis ## Footnote Their expression order mirrors their chromosomal order.
55
How does the human embryo differ from the mouse embryo at the point of implantation?
The human embryo forms a flat, disc-shaped epiblast instead of a cup-shape ## Footnote Despite morphological differences, the underlying processes are similar.
56
What is the 'Day 14 Rule' in the UK regarding human embryos?
A law that prevents culturing human embryos beyond 14 days of development ## Footnote It is based on ethical considerations and the point of individualisation.
57
What is the Carnegie Collection?
A collection of human embryos used to study early human development ## Footnote It has significantly contributed to understanding human embryology.
58
What is the significance of the first 13 days of human development?
We have a reasonably good understanding of human development during this period, particularly from IVF samples.
59
What is referred to as the 'black box' of human development?
The gap in knowledge between the first 13 days and week 4 of human development, particularly where gastrulation occurs.
60
What is morphogenesis?
The process of shaping and forming distinctive structures and organs in an organism.
61
What is neurulation?
The process of forming the neural tube, which is a precursor to the central nervous system (CNS).
62
What is the role of the notochord in neural tube development?
It provides signals that create a gradient to pattern the developing neural tube.
63
What are median hinge points (MHP) in neural tube development?
Cells that constrict at the top compared to the bottom, acting like a hinge for tissue shape change.
64
What are dorso-lateral hinge points (DLHPs)?
New hinge points created by compacted tissue at the edges of the neural plate.
65
What is the significance of the Shh signaling molecule?
It creates a concentration gradient necessary for differentiating dorsal and ventral cell fates in the neural tube.
66
What are Neural Tube Defects (NTDs)?
Congenital abnormalities arising from the failure of the neural plate to close completely.
67
What is somitogenesis?
The process of forming somites, which are blocks of tissue that develop into vertebrae, muscles, and skin.
68
How are somites formed in the embryo?
They are derived from the paraxial mesoderm and appear sequentially in an anterior-to-posterior order.
69
What is the segmentation clock?
An internal feedback loop in cells of the pre-somitic mesoderm that oscillates between high and low levels of Hes/Her gene expression.
70
What role does Notch signaling play in somitogenesis?
It couples nearby cells, synchronizing their oscillation cycles in the segmentation clock.
71
What is the clock-and-wavefront model?
A model that combines local oscillation of gene expression and global signaling gradients to govern cell fate decisions.
72
What are the effects of genetic changes on the segmentation clock?
Small genetic changes can lead to significant differences in the dynamics of the segmentation process.
73
What is an example of evolutionary plasticity in somitogenesis?
Differences in segmentation clock speed can lead to morphological differences between species.
74
How can researchers model somitogenesis in vitro?
By differentiating mouse and human ESCs towards PSM lineages to observe oscillations and coordination.
75
What are the key stages of mammalian development discussed?
* Pre-implantation stages * Implantation * Gastrulation * Development of body plan structures
76
What is the importance of pluripotent stem cell systems in studying development?
They allow us to model normal and abnormal developmental states in both mice and humans.

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