Gastrulation/germ cells Flashcards
What do germ cells give rise to?
Eggs and sperm
What is the ‘stem cell niche’?
A microenvironment that protects the stem cells
What is a zygote?
A fertilised egg that can give rise to ALL the cells of the body - INCLUDING the placenta
Describe the restriction in potency from the zygote –> embyro
1) Zygote potency is RESTRICTED to give rise to EITHER:
- Embyro
- Extra-embyronic tissues
2) Restricted further in the embryo, to give rise to either:
- Endoderm
- Ectoderm
- Mesoderm
3) Restriction into finer fates, eg:
- In the mesoderm - give rise to certain MESODERM components
Where does cell fate restriction and differentiation take place?
In all 3 germ layers
Where do all the cells in the organs come from?
How?
One of the 3 germ layers - gradually restrict fate
What are the different names of the potency stages?
TOTIpotent (give rise to ALL cells - even placenta)
PLURIpotent (give rise to ALL cells, but the placenta)
MULTIpotent (give rise to all of the cells of a cells of a specific germ layer)
What happens to multipotent cells eventually?
What does this form?
When?
They DIFFERENTIATE
Begins to form the body axes and beginning of tissues
In the first 3 weeks post fertilisation
What builds the organs of the body?
When?
Many signalling events
By week 8 pf
During development, how and why are some cells set aside?
TWO SETS are set aside in an UNDIFFERENTIATED state
For:
1) Regeneration and restoration of the individual over its lifetime
OR for:
2) The NEXT generation
What are the two sets undifferentiated cells that are set aside during development called?
1) ADULT stem cells/ tissue specific stem cells
2) GONADAL germ cells
What are the gonadal germ cells?
What are they required for?
Specialised TOTIPOTENT cells set aside in the GONADS in an undifferentiated state for the next generation
Required to maintain the species
Where do gametes arise from?
Gonadal germ cells
Where do gonadal germ cells arise from?
Primoridal germ cells that have migrated into the gonads to become the progenitors for eggs and sperm
Where do primordial germ cells arise from?
NOT in the gonads
Arise from the EXTRA-EMBRYONIC MESOENDODERMAL cells
And migrate into the gonads
How are primordial germ cells specified?
Through autonomous and non-autonomous signalling
Where do the gonads arise from?
Mesoderm/endoderm
What is essential for reproductive success?
The establishment of a GONADAL stem cell NICHE
What can the somatic cells of flatworms form?
New organisms
Where are the primordial germ cells specified?
In a SPECIFIC location on the ‘edge’ or ‘outside’ of the developing embryo
What is needed for germ cell differentiation?
1) A PLASTIC cell type (totipotent)
2) A cell capable of undergoing MEIOSIS
How is the diploid status of the cells of the body maintained?
By maintaining the germ cells are HAPLOID
Describe the development of the nematode
- Starts from ONE cell
- Asymmetrical divisions produce a SMALLER specialised cell (called the P cell)
- P cell inherits a different set of cytoplasmic determinants
- Happens MULTIPLE times
- P cell sits at the POSTERIOR of the embryo and is maintained during each cell division
Why is the nematode an advantageous model for the setting aside of the germ line?
Can follow EVERY cell division
EVERY cell can be names
How is the P cell different to the other cells?
Due to the orientation of the CELL DIVISION PLANE - determines the fate of the daughter cells:
Along the vertical plane:
- 2 identical cells
- Idenitcal to the mother
How is the P cell different to the other cells?
Due to the orientation of the CELL DIVISION PLANE - determines the fate of the daughter cells:
Along the vertical plane:
- 2 identical cells
- Identical to the mother
- Maintain stem cell pool
Along the horizontal plane:
- 2 DIFFERENT daughter cells
- Progenitor and a cell with different determinant that go onto DIFFERENTIATE
How is the stem cell pool maintained with the orientation of the cell division plane?
Along the vertical place
What does the P cell acts as?
A ‘PRE-germ’ cell
Through asymmetrical cell division, what does the P cell ALWAYS inherit?
What are these?
Always inherits P granules
A MIX of PROTEINS and RNAs - in the cytoplasm but can enter into the nucleus
What 3 things do the P granules do?
1) Bind to DNA of the P-cell and block ALMOST all transcription –> blocking differentiation
2) Block TRANSCRIPTION in the cytoplasm –> no functional proteins, therefore no behaviour
3) Promote STEM CELL FATE and cause the cells to undergo meiosis (rather than mitosis)
How do the P granules maintain stem cell fate?
They prevent the transcription of all genes (no differentiation)
APART FROM the genes that promote ‘stem-ness’ –> these genes are transcriptionally ACTIVATED by the P-granuels
Where do P granules lie?
ALWAYS in the POSTERIOR part, just outside the developing embryo
Where are P cells and P granules present?
In the NEMATODE
What are the equivalent to P cells in the xenopus?
What do these cells express?
Germ cells
Express NANOS gene
What does NANOS do in the Xenopus?
Translated into a protein and blocks transcription/translation of other proteins
Allows the transcription of cells promoting ‘stemness’
What do the established germ cells in all vertebrates show?
- Little transcription/translation
- NO differentiation
- Few active genes
What do the few genes that are active in germ cells do?
What does this provide the cell with?
Either:
- BLOCK transcription and translation
OR
- PROMOTE stemness –> provides the cell with a plastic identity
How are PGS shut down transcriptionally/translationally?
Through EPIGENETIC SILENCING mechanisms:
- DNA methylation
- Recruits transcriptional repressors
OR
Through HISTONE REMODELLING:
- Histones pack closely together making it difficult for the gene to be accessed
When are PGCs made?
In the first 2 months pf
Where do the PGCs sit when they are made?
Just below what is the future rectum/anus (posterior part of the hindgut)
What happens to the position of the PCGs as the body axes form?
What happens to them here?
They remain below the posterior part of the hindgut
Here:
- They are protected from DIFFERENTIATION signals
What divisions are PGCs capable/not capable of?
Capable of meiotic
NOT capable of mitotic
When do the PGCs begin to migrate into the embryo?
How is this seen?
At 8 wpf - once rapid differentiation of early embryogenesis begins to decrease
Seen in studies of drosophila
What is the PGC called in drosophila?
What gene do these cells transcribe?
POLE cells
Transcribe the gene Vasa
How doe the PGC migrate?
1) Attach to the gut tube and migrate through the gut
2) Reach the MIDGUT - leave and move sideways into the future gonads
What are the PGCs protected by in the future gonads?
By the GONADAL NICHE:
- Specialised microenvironment
In drosophila, what happens to the pole cells in the gonadal niche?
When?
DIVIDE: at the larval stage
DIFFERENTIATE: at metamorphosis - to give rise to eggs or sperm
What determines if the PGCs differentiate into eggs or sperm?
The microenvironment:
- If ovary or testies-like
- Specific cells in the micro environment cause the differentiation into eggs or sperm
In drosophila, what do the cells attach to in the ovaries?
Stromal cap
In drosophila, what do the cells attach to in the testies?
Hub cells
Describe the full pathway of the PGCs in the chick/mouse/human
1) PGC stay out of the embryo (in extra-embryonic territory) whilst the major instructive events of the body (body axis formation)
2) PGCs them migrate though the posterior gut (hindugut) and
3) Leave the gut where the hindgut meets the midgut and move LATERALLY to the genital ridges
4) Find themselves in the gonadal niche
What are the genital ridges?
Where are they found?
The PRECURSOR to the gonads
Found either side of the gut tube
How do the PGCs find their way to the the gonads?
1) Have INTEGRINS with bind to fibronectin - allowing the cells to follow a FIBRONECTIN trail through the gut
2) Genital ridges secrete a CHEMOATTRACTANT to guide the PGC laterally
Where do the genital ridges arise from?
From the INTERMEDIATE mesoderm
Describe the interaction between the genital ridges and the PGCs
Interact through RECIPROCAL INDUCTIVE INTERACTIONS
To produce a specialised microenvironment (gonadal niche) that goes on to form the gonads
What does the gonadal niche do?
PROTECTS the PGCs in their TOTIPOTENT state
AND THEN
SUPPORTS their meiotic divisions and the formation of either eggs or sperm
What is it possible to make eggs or sperm from?
Fibroblast - dedifferentiate into PLURIPOTENT cell state and direct it into a PGC
PGC –> eggs or sperm
What must PGCs be protected from as they migrate through the gut?
How is this done?
Must be protected from differentiation signals
By a ‘travelling stem cell niche
- Travelling with SUPPORT CELLS that maintain the stem cell fate
- By secreting stem cell factor (SCF)
What happens if the support cells that travel with the PGC through the gut are removed?
- Removal of the STC/chemoattractant
- PGCs no longer protected from differentiation signals and may get stuck in the gut (not attracted to the gonads)
What does the failure of the PGCs to migrate to a protective niche or the loss of SCF cause?
PGCs to differentiate - forming a teratoma
