15. Embryonic Development Flashcards
Give some reasons for studying embryology?
- Model system for cell/molecular biology
- Understanding congential defects
- Model for regenerative medicine
What are some model systems used in embryology?
- Xenopus (frog)
- Chick
- Mouse
- C elegans
- Zebrafish
Give an example of a gene that is conserved between species.
- Pax6 is conserved in humans, mice, zebrafish and drosophilia
- A mutation in the Pax6 gene results in eyeball abnormalities in all of these species
Name some advantages of the fly as a model system for embryology.
- Cheap
- Short lifespan
- Easy to manipulate
Name some advantages of the mouse as a model system for embryology.
- Foremost mammalian model
- Short gestation period
- Highly similar development to humans
Name some advantages of C elegans as a model system for embryology.
- Cheap
- Have fixed no. of cells -> Exact development + position of each cell has been mapped
Name some advantages of the chick as a model system for embryology.
- Accessible -> Grows in eggs
Name some of the important aspects of development.
- Cell differentiation
- Patterning
- Induction
- EMT and MET (epithelial to mesenchymal transitions and mesenchymal to epithelial transitions)
- Morphogenesis
- Cell death
Are signalling pathways ever reused in the development?
Yes, the same signalling pathways appear in many places in the human body.
What are the main important stages in embryonic development?
- Fertilisation (Day 0)
- Pre-embyronic stage (Day 0)
- Implantation
- Bilaminar germ disc
- Embryonic period (3rd week)
- Gastrulation + Axis formation
- Neurulation
- Embryonic folding
- Somitogenesis
- Limb bud formation
- Organogenesis
- Fetal period (8th week)
- Growth
- Maturation
- Birth
What is the product of fertilisation?
Diploid zygote
Define fertilisation.
The joining of an egg and sperm to produce a diploid zygote.
Describe the process of fertilisation.
- Occurs in ampullary region of oviduct (the far end, near the ovary) – Note: Oviduct = Fallopian tube
- In order to fertilise oocyte, spermatozoa need:
- Removal of glycoprotein coat (capacitation) -> This is calcium dependent
- Binding to zona pellucida -> Activates acrosome reaction, where acrosome (a Golgi-derived organelle in the head of the spermatozoon) releases enzymes to break through the zona pellucida
- As spermatozoon enters the zona pellucida, the membrane of the spermatozoon fuses with the membrane of the oocyte, releasing the spermatozoon nucleus into the oocyte
- At the same time, the cortical granules of the oocyte release their contents, making the zona pellucida impenetrable to other spermatozoa
- Entry of the spermatozoon nucleus stimulates the oocyte to complete the second meiotic division (meiosis has not yet been completed) -> It is now called a definitive oocyte and the two nuclei are called the female pronucleus and male pronucleus (the name for the nucleus during fertilisation)
- Since it has been fertilised, the definitive oocyte can also be called the zygote
- The two pronuclei approach each other and duplicate their DNA, ready for the first mitotic division
- Pronuclear membranes break down and the chromosomes line up for metaphase
- First cell division takes place
What percentage of sperm reach the cervix and what happens to them there?
- About 1%
- Ovulation induces them to move further into the oviduct
What are the technical names for the sperm and egg?
- Sperm = Spermatozoon (pl. spermatozoa)
- Egg = Oocyte
Where does fertilisation occur?
Ampullary region of oviduct (a.k.a. fallopian tube)
(far end, near the ovary)
Draw out the path of spermatozoa to the oocyte.
What two things must happen in order for the spermatozoon to enter the oocyte?
- Removal of glycoprotein coat (capacitation) -> This is calcium dependent
- Binding to zona pellucida -> Activates acrosome reaction, where acrosome (a Golgi-derived organelle in the head of the spermatozoon) releases enzymes to break through the zona pellucida
What prevents multiple spermatozoa fertilising the oocyte?
Cortical granules (just inside the plasma membrane) release their contents, making the zona pellucida impenetrable.
Describe the process of meiosis involved in generating the female pronucleus.
- The process of meiosis is halted just before the second meiotic division
- When the male pronucleus enters the oocyte, this triggers the second meiotic division -> This creates the female pronucleus
How is the first mitotic division different to normal mitotic divisions?
The DNA duplication occurs before the male and female pronuclei even fuse.
What are pronuclei?
The nuclei of the gametes during the process of fertilisation.
Draw a diagram of an oocyte and spermatozoon.
What is a zygote?
The union of the sperm cell and the egg cell. Also known as a fertilized ovum.
What is cleavage?
A series of mitotic divisions without cell growth.
Describe the process of cleavage.
- Cleavage is a series of mitotic divisions without cell growth
- All of the cells during cleavage are called blastomeres
- Cleavage occurs with all of the cells still within the zona pellucida, while travelling down the oviduct
- At the 8 to 16 cell stage, outer cells begin to form tight junctions with each other, which is called compaction -> This leads to the morula structure
- Morula (from the Latin for mulberry) -> 16 to 32 cells
- Inner cell mass (ICM) (a.k.a. embryoblast) -> On the inside of the morula -> Loses totipotency so can only form embryo
- Trophoblast -> On the outside of the morula -> Keeps totipotency and goes on to form placenta
- Blastocyst (not to be confused with blastula: blastocyst is what a blastula is called in mammals)
- Blastocystic cavity (a.k.a. blastocoel) -> Formed by the absorption of fluid
- Inner cell mass (ICM) (a.k.a. embryoblast) -> Is forced to one side of the cavity as a compact mass
- Trophoblast -> Is now a single-layered epithelium around the outside
- The zona pellucida degenerates and the blastocyst is able to hatch out
What are the cells in a cleaving morula or blastocyst called?
Blastomeres
What is compaction?
In the 8 to 16 cell phase of cleavage, outer cells start to form tight junctions with each other.
What are the different structures seen during cleavage? Draw diagrams.
- Morula (from the Latin for mulberry) -> 16 to 32 cells
- Inner cell mass (ICM) (a.k.a. embryoblast) -> On the inside of the morula -> Loses totipotency so can only form embryo
- Trophoblast -> On the outside of the morula -> Keeps totipotency and goes on to form placenta
- Blastocyst (not to be confused with blastula: blastocyst is what a blastula is called in mammals)
- Blastocystic cavity (a.k.a. blastocoel) -> Formed by the absorption of fluid
- Inner cell mass (ICM) (a.k.a. embryoblast) -> Is forced to one side of the cavity as a compact mass
- Trophoblast -> Is now a single-layered epithelium around the outside
Clinical relevance: Describe the different types of twins and how they arise.
- Dizygotic twins -> Two seperate blastocysts, which form embryos that may have a fused placenta but do not share blood supply
- Monozygotic twins I -> ICM splits, which form embryos that have a common placenta and sometimes share a blood supply
- Monozygotic twins II -> Splitting occurs anywhere between two-cell to morula stage, which form embryos that may share placenta but do not share blood supply
Give some examples of the clinical relevance of fertilistaion and cleavage.
- Twins
- IVF
- Cloning
- Embryonic stem cells
When does the developing embryo lose the zona pellucida?
- After it is a blastocyst
- Blastocyst ‘hatches’ from the disintegrating zona pellucida around day 5
- This allows for implantation
Describe the process of IVF.
- Hormonal stimulation of mature oocyte formation produces several mature follicles
- Collection of oocytes
- Placement in Petri dish and fertilisation in vitro
- Cleavage of zygotes in medium until 4 to 8 cell stage is reached
- Transfer to up to 5 embryos into uterine cavity using a catheter
During implantation, what does the blastocyst adhere to?
Endometrium (uterus wall)
Describe the process of implantation. Draw diagrams.
- Morula reaches uterus by day 3/4 of development
- Blastocyst hatches from zona pellucida and adheres to endometrium lining (uterus wall)
- This triggers decidual reaction: endometrial stroma (connective tissue) responds to blastocyst and progesterone from the corpus luteum and turns into decidual cells (secretory cells) -> These secrete lots of glycogen and mucus for immunological protection
- The uterine wall becomes more vascularised and oedematous (swollen)
- Trophoblast near the uterus begins to grow into the uterine wall, forming a syncytiotrophoblast that starts pulling the blastocyst into the uterine wall
What is the decidual reaction?
It is part of the implantation process:
- The stroma (connective tissue) in the endometrium responds to binding of the blastocyst as well as progesterone from the corpus luteum
- Stroma cells differentiate into decidual cells (secretory cells) -> These secrete lots of glycogen and mucus for immunological protection
Give some clinical relevance of implantation.
Ectopic pregnancy:
- When a blastocyst implants outside the uterus, for example in the pericardial cavity or on the surface of the oviduct, the epithelium coming in contact with the blastocyst will still react, becoming more vascularised
- This allows the blastocyst to survive outside the uterus and start to develop, but it will not reach term
- This may be threatening to the mother due to, for example, haemorrhage
What does the trophoblast do during implantation?
- At one pole of the trophoblast, the syncytiotrophoblast and cytotrophoblast form from trophoblast cells
- Syncytiotrophoblast cells are the cells that initially invade the endometrium, drawing the blastocyst into the uterine wall -> Ruptures capillaries so creating an interface between maternal blood and embryonic fluid for passive transfer. Also secretes a lot of hCG to maintain corpus luteum
- Cytotrophoblast cells line the inside of the syncytiotrophoblast and will eventually form the foetal portion of the placenta
What things trigger the decidual reaction?
- Progesterone from the corpus luteum
- HcG from the synctiotrophoblast assists with this by maintaining the corpus luteum
What are hydratidiform moles and what are the two main types? [EXTRA]
- Growth of an abnormal fertilized egg or an overgrowth of tissue from the placenta
- Embryos derived from two male haploid genomes (androgenotes) give rise to largely placental tissue
- Embryos derived from two female pronuclei (gynogenotes) give rise to largely embryonic tissue
What is the first structure that is formed after implantation?
Bilaminar germ disc
What does the bilaminar germ disc form from?
Inner cell mass (ICM)
What are the two layers of the bilaminar germ disc?
- Hypoblast
- Epiblast
What are the two cavities that surround the bilaminar germ disc?
- Amniotic cavity
- Yolk sac
Which layer of the bilaminar germ disc gives rise to the amnion and which gives rise to the yolk sac?
- Epiblast -> Amnion
- Hypoblast -> Yolk sac
What is the amnion and amniotic cavity?
- The amnion is a membrane that closely covers the embryo when first formed.
- It fills with the amniotic fluid which causes the amnion to expand and become the amniotic sac which serves to provide a protective environment for the developing embryo or fetus.
Which cell group forms the placenta?
Trophoblast
Describe the formation of the amniotic cavity and yolk sac.
Amniotic cavity:
- Develops between the epiblast and cytotrophoblast
- Cells from the epiblast form amnioblasts that line the cavity -> This is called the amnion
- The amniotic cavity will eventually engulf the entire embryo
Yolk sac:
- Cells from the hypoblast migrate out in the two waves
- Wave 1: Forms the primary yolk sac
- The exocoelomic (Heuser’s membrane) that lines the primary yolk sac is formed by the migrating hypoblast cells
- Wave 2: transforms the primary into the secondary yolk sac
After initial implantation by the synctiotrophoblast and cytotropohblast, how does the embryo implant further?
- The emrbyo keeps embedding further into the endometrium until the cytotrophoblast surrounds the embryo and a coagulation plug is formed
- Vacuoles in the synctiotrophoblast cells fuse to give lacunae
What are the extraembryonic mesoderm and how does it form?
- The extraembryonic mesoderm is the layer of mesoderm that forms just inside of the cytotrophoblast (between the cytotrophoblast and amnion + lining of primitive yolk sac)
- It is formed by the migration of cells from the edges of hypoblast and epiblast
What are the chorionic cavity and how does it form?
- Chorionic cavity = Extraembryonic coelom
- It is the cavity that forms within the extraembryonic mesoderm, between the cytotrophoblast and the embryo
Describe how the secondary yolk sac forms from the primary yolk sac. What structures form alongside this?
- The trophoblast grows much faster than the bilaminar disc
- This gives rise to the chorionic cavity and secondary yolk sac
- The connecting stalk left behind forms the umbilical cord
What happens to the lacunae in the synctiotrophoblast?
They fill with blood due to the decidual reaction prompting greater vascularity.
Summarise the main events just after implantation, up to the formation of the secondary yolk sac.
Implantation:
- Morula reaches uterus by day 3/4 of development
- Blastocyst hatches from zona pellucida and adheres to endometrium lining (uterus wall)
- At one pole of the trophoblast, the syncytiotrophoblast and cytotrophoblast form from trophoblast cells:
- Syncytiotrophoblast cells are the cells that initially invade the endometrium, drawing the blastocyst into the uterine wall -> Ruptures capillaries so creating an interface between maternal blood and embryonic fluid for passive transfer
- Cytotrophoblast cells line the inside of the syncytiotrophoblast and will eventually form the foetal portion of the placenta
- The decidual reaction is triggered by progesterone from the corpus luteum and hCG from the synctiotrophoblast assists with this by maintaining the corpus luteum
- Decidual reaction: Endometrial stroma (connective tissue) turns into decidual cells (secretory cells) -> These secrete lots of glycogen and mucus for immunological protection
- The uterine wall becomes more vascularised and oedematous (swollen)
- Bilaminar germ disc forms from the ICM -> The two layers are the hypoblast and epiblast
Amniotic cavity forms from the epiblast:
- Develops between the epiblast and cytotrophoblast
- Cells from the epiblast form amnioblasts that line the cavity -> This is called the amnion
- The amniotic cavity will eventually engulf the entire embryo
Yolk sac forms from the hypoblast:
- Cells from the hypoblast migrate out in the two waves
- Wave 1: Forms the primary yolk sac
- The exocoelomic (Heuser’s membrane) that lines the primary yolk sac is formed by the migrating hypoblast cells
- Wave 2: transforms the primary into the secondary yolk sac
Later implantation:
- The embryo keeps embedding further into the endometrium until the cytotrophoblast surrounds the embryo and a coagulation plug is formed
- Vacuoles in the synctiotrophoblast cells fuse to give lacunae -> These fill with blood due to increased vascularity
- The extraembryonic mesoderm is the layer of mesoderm that forms just inside of the cytotrophoblast (between the cytotrophoblast and amnion + lining of primitive yolk sac) -> It is formed by the migration of cells from the edges of hypoblast and epiblast
- The trophoblast grows much faster than the bilaminar disc
- This gives rise to the chorionic cavity and secondary yolk sac
- The connecting stalk left behind forms the umbilical cord
Compare the body axes in the adult and embryo.
What does the epiblast give rise to eventually?
All embryonic tissues.
What is gastrulation?
A complex series of movements during which the three germ layers establish their appropriate topological positions and the basic body plan emerges.
What are germ layers?
An operational definition describing three cell layers/types that give rise to different organ systems in the body.
What germ layer are mesenchymal cells derived from?
- Mesenchymal cells can derive from any germ layer
- They form a loosely organised tissue, which frequently differentiates subsequently into specific cell types (eg. mesenchymal cells of the sclerotome will form the vertebral column); mesenchymal cells in skull development
What are the 3 definitive germ layers?
- Ectoderm (on the side of the amniotic cavity)
- Mesoderm
- Endoderm
Describe the process of gastrulation.
- Gastrulation begins with the formation of a primitive streak, which is a shallow marked line along the epiblast.
- This begins at what is now defined as the caudal end of the epiblast and runs along the midline.
- At the cranial (or rostral) end of the streak, a circular region called the primitive node forms, which contains a depression called the primitive pit.
- This depression continues down the primitive streak, forming a long, linear primitive groove. The primitive groove along with the primitive pit mark sites to which epiblast cells migrate and travel towards the mesoderm (a process known as ingression), beginning the process of creating a trilaminar embryonic disc.
- Endoderm is formed by the invasion of the hypoblast. Cells leaving the primitive streak displace the hypoblast cells and gradually form the endoderm.
- Mesoderm forms when the epiblast cells migrate laterally or cranially after passing through the primitive groove, before they reach the endoderm. This forms a layer of cells between the endoderm and the epiblast. A
- Ectoderm is essentially what remains of the epiblast after gastrulation is complete.
What gastrulation begin with?
Begins with the formation of a primitive streak, which is a shallow marked line along the epiblast.
Describe how gastrulation defines the body axis.
- Gastrulation begins with the formation of a primitive streak, which is a shallow marked line along the epiblast.
- This occurs at what is now defined as the caudal end (relating to the “tail) of the epiblast.
- Aside from determining the cranial-caudal axis, the streak is defined as running as medially as possible, so the medial-lateral direction is perpendicular to this.
- Right and left are also defined when looking down at the ectoderm from the amniotic fluid, when the caudal end is closest to the viewer.
What does the primitive node act as?
An organiser.
What determines what an ingressing cell passing through the primitive streak becomes?
The time at which it passes past the primitive node and through the primitive streak.
What are some defects in primitive node and streak activity?
What transition do cells undergo when they ingress during gastrulation?
EMT (epithelial-to-mesenchymal transition)
Which direction does the primitive streak move in during gastrulation?
Caudally
What are the two broad categories of structure that the ectoderm goes on to form?
What is neurulation?
The formation of the neural tube.
Describe neurulation.
- The notochord (in the mesoderm) along the midline induces the ectoderm above it to differentiate into the neural plate
- The neural plate folds downwards so that the two sides of it fuse
- This produces a tube called the neural tube
- The cells just above it are called the neural crest
What transition do neural crest cells undergo?
EMT (epithelial to mesenchymal transition)
What is the neural plate?
The area of ectoderm along the midline that goes of to form the neural tube.
What induces neurulation?
Notochord (in the mesoderm just below the neural plate)
What are two examples of neural tube closure defects?
In summary, what does the nervous system form from? [IMPORTANT]
Neuroectoderm
What are the derivatives of the neural tube?
CNS
Summarise the derivatives of the neural crest. [IMPORTANT]
- PNS
- Dorsal root ganglia
- Autonomic ganglia
- Cranial nerve ganglia
- Enteric nervous system
- Schwann cells
- Skin -> Melanocyte
- Cranial bones
- Eyes
Give an example of a condition caused by failure of neural crest cell migration.
In general, summarise the different types of tissue that mesoderm goes on to form.
- Muscle
- Connective tissue
- Blood, etc.
What are the different types of mesoderm?
- Prechordal (head)
- Axial (notochord)
- Paraxial (somites)
- Intermediate
- Lateral plate
What is another name for the notochord?
Axial mesoderm
What are some roles of the notochord?
- Induces the neural plate (and therefore neural tube)
- Patterns the neural tube in the dorso-ventral axis
- Forms primitive axis around which axial skeleton is laid down
What does the notochord go on to form? [IMPORTANT]
Nucleus pulposus of intervertebral discs
How are the neural tube and associated structures patterned in the craniocaudal axis?
Check this -> Thought it was Hox genes but it might be Shh