Lecture 2: Early Embryo Development

Learning Objectives: Definitions, Key Events During Early Embryo Development, Examples of stem cell/progenitor populations that drive embryo development

Define Cell Lineage

Developmental history of differentiated cell traced back to first cell it arose from

Define Blastomere

cell type generated by zygote cleavage

Define Blastocyst

spherical embryo at time of implantation consisting of three tissue types: trophoectoderm, epiblast and primitive endoderm

Define Trophoectoderm

The precursor of the placenta

Define Epiblast

founding tissue of embryo proper, gives rise to all foetal cells

Define Primitive Endoderm

Extraembryonic tissue, initially covering epiblast surface, later gives rise to the yolk sac tissue

Define Inner Cell Mass

precursor to the epiblast and primitive endoderm

Define Potency

Ability of a cell to differentiate into one or more cell types

Define Totipotency

Ability of a cell to give rise to fully functional organism (both embryonic and extraembryonic tissues)

Define Pluripotency

Ability of a cell to develop into all embryonic (but not extra embryonic) cell types including the germ cells

What are the two hallmarks of pluripotency?

(i) Expression of pluripotent transcription factors (descriptive) (ii) Tertratocarcinoma formation (functional)

How can we examine pluripotency transcription factors and what does this tell us?

Through RNA in situ hybridisation and a colour metric assay. The dark region indicates pluripotent factors, indicating that the cell is pluripotent

How can teratocarcinoma formation evidence pluripotency

Pluripotent cells grafted onto kidney of host mouse, gives rise to tetratocarcinomas

What does the ectoderm differentiate into?

skin, peripheral and central nervous system

What does the Mesoderm differentiate into?

blood, heart, muscle, kidney, skeleton

What does the endoderm differentiate into?

The gut and internal organs

What are the four key pluripotency transcription factors discussed in this lecture?

Nano, Oct4, Sox2, Bra

Does the trophooectoderm or the inner cell mass contain the pluripotent cells?

The inner cell mass

How does cell lineage specification during gastrulation take place?

Regionalised manner, distinct signals, lineage-specific transcription factors

Which stage marks the onset of cell type specification?

Gastrulation

Describe the formation of the primitive streak

Cells proliferate and move from anterior to posterior coupled with gastrulation

Which transcription factor marks the future head?

Otx2

Which transcription factor marks the posterior axis?

Bra

Why are DKK1 and Cerberus “Head inducers”

act as antagonists to the Wnt pathway (which would push cells to posterior fates)

Define “falling off a cliff” in primitive streak formation

The epithelial to mesenchymal transition which allows cells greater mobility and drives the reorganisation of the embryo into the three germ layers

What are neuromesodermal progenitor’s characteristics?

• Biopotent cells

• Found in posterior embryo

• Building blocks of paraxial mesoderm

• Precursors of future veretebral column, skeletal muscle and cartilage

What signalling activities are elevated in the NMP niche?

WNT and FGF

What are neuralmesodermal progenitors important for?

Embryo body elongation

What indicates the emergence of neuromesodermal progenitors?

SOX2 and Bra co-expression

Describe how Bra and Sox2 determine NMPs specialisation

In spinal cord cells bra is down regulated and Sox2 is unregulated. In paraxial mesoderm, bra is unregulated and Sox2 is down regulated.

Describe the type of developmental abonormalitites which can result from NMP defects (some cows spook suddenly)

Spina bifida, currarino syndrome, sacral genesis, spondylocostal dysostosis (vertebral and spinal abnormalities)

Briefly outline neurilation

• neural crest is multipotent

• signalling pathway activates cascades of transcription factors that are important for neural crest formation

• Cells undergo epithelial to mesenchymal transition and migrate to neural crest

• The cells then give rise to a variety of different cell types (200 to 300)

Where is the sacral part of the neural crest located and what does it give rise to?

located at the very bottom of lumbrosacral part, contributes to the enteric nervous system innervating the most posterior part of the gut

What does the anterior (cranial) part of the head give rise to?

• Craniofacial Skeleton

• Cranial ganglia

• Teeth

• Thyroid cells

What does the posterior (vagal) part of the head give rise to?

• Enteric ganglia (GI tract)

• Smooth muscle cells

• Cardiac septa (heart development)

What does the trunk of the NC give rise to?

• dorsal root gangila

• sympathetic ganglia (pain preceptors, innervating visceral organs)

• adrenal medulla

What are defects in NC specification called?

Neurocristopathies

What are neural stem cells characterised by?

self renewal in their niche, bipotency, characterised by ETF and FGF presence

What are glia important for?

supporting axon of neurons

Name the STEM cell which gives rise to all blood cell types

Haematopoietic

Describe the experiment that shows that HSCs can reconstitute the entire haematopoietic system

sub-lethal radiation to abolish hematopoietic stem cell system in mice, transplanted HSCs in, Haematopoietic system was rescued

Which signals are important for primitive streak formation (anterior to posterior)? (wailing babies (are) frequently noisy)

WNT, BMP, FGF, Nodal

Why is gastrulation significant?

onset of cell type specification

Why are neural stem cells described as bipotent

because they can differentiate into neurons and glia