DEV Flashcards
What is the rate of children born a ‘birth defect’?
1:33 babies have a “birth defect” which must be treated/managed
(this is live births only- many more case miscarriage)
What is hypospadia?
A misplaced urethral opening in males
Where does fertilization occur in the FT?
The most distal region
What are the 5 stages of embryonic development
- Early Blastocyst Formation
- Blastocyst Split
- Two Germ layer Stage
- Three Germ Layer Stage
- Extra-embryonic tissue
What occurs during early blastocyst development?
- Egg fertilized -> uterus [dividing on the way 1 division/24 hours]
- Morula = Ball of cells = -> 16 cell stage after 3 days
- Blastocyst = Cell Mass -> at 4 days.
- On 4th day Blastocyst undergoes cavitation to form a cavity -> Blastocoele
- Blasotcyst is asymmetrical with more cells up the top.
- Called the ‘ Inner cell mass’
What are the two types of cell in the blastocyst?
Outer epithelial layer (trophoblast)
- Forms extra embryonic structures like placenta.
Inner cell mass
- Forms embryo
At what stage of development does the blastocyst implant into the uterine wall?
Between days 5 and 10
What happens during the two germ layer stage?
- Inner cell mass splits to form the:
- Bilaminar Disk = Epiblast above and Hypoblast below
- Embryo forms from part of the epiblast
- Rest of the epiblast and all of the primitive hypoblast give rise to extra-embryonic tissues
What does the hypoblast from?
It bgins to surround the blastocoele - it is called the yolk sac though it does not have any yolk in humans
What does the epiblast form?
- Forms a cavity called the Amniotic Sac.
- Upper cells form the roof
- Lower cells will form the embryo
- Embryo will form at the point of overlap b/w Yolk Sac and Amniotic Sac
What are three germ layers and what do they form?
Ectoderm - nervous system and epidermis
Endoderm - epithelium of gut and associated organs
Mesoderm - blood, hear, kidneys, gonads, most bones, muscles and CT, urinary tract, haemopoetic tissue, pleura, peritoneum, pericardium and NOTOCHORD
How does the Notochord form and what does it do?
The notochord forms in the mid-line (the location of the vertebral column). The notochord runs the length of the embryo and gives it its axis. its used as a landmark for other structures and produces chemical signals do drive development in the surrounding structures.
The Notochord induces the overlying ectoderm to form the neural plate which in turn forms the neural groove which folds in on itself to give the neural tube. The neural tube runs the length of the embryo and become the brain and spinal cord.
What is the neural crest?
The cells at the top of the neural tube form the neural crest. These are ectodermal cells which migrate away from the neural tube to contribute to a wide range of structures. The first thing they do is separate the neural tube from the ectoderm
What are the neural crest derivatives and what happens if these cell fail to migrate properly?
Dorsal root ganglia • Sympathetic and parasympathetic ganglia • Enteric ganglia • Schwann cells • Melanocytes • Dentine • Muscle, cartilage and bone of skull, jaws, face and pharynx
Cells are heading for the midline of the face, they come from the back (of the face) and migrate around. Failure to do so properly can cause cleft lip and palate (1:1000)
This occurs in the 4-5th week of life when too few cell end up in the midline
What is the difference between mesoderm and mesenchyme?
Mesoderm
• Mesoderm is one of the three embryonic tissue types (origin)
Mesenchyme
• Mesenchyme refers to the shape and behavior of the cells
• Can be of ANY origin, but often mesodermal origin
• If Cells are MESENCHYMAL they lose contact with one another and move independently and alone
• If Cells are EPITHELIAL they are closely bound together.
- Cancer is a conversion to a mesnechymal cell (i.e. which allows metastasis)
What are the three types of mesoderm?
1) Paraxial
2) Intermediate
3) Lateral
What does paraxial mesoderm from?
Closest to Midline
(i) Dermis of skin
(ii) Axial skeleton
(iii) Axial and limb buds
What does intermediate mesoderm from?
In Between
• Urogenital system (kidneys + tubes)
What does lateral mesoderm from?
Closest to the Edge
1) Ventrolateral body wall
2) Visceral pleura, peritoneum
3) Blood vessels and blood forming tissue
4) Heart
5) Wall of gut and respiratory tissue
What are somites and how do they form?
- Somitomeres -> Swellings appear progressively down length of paraxial mesoderm, on either side of the Neural Tube.
- At the 20 somitomere stage, the 8th pair of somitomeres becomes an independent pair of somites.
- Somite is a free somitomere.
What happens to the somitomeres above and below 8?
- After the 8th changes, the 9th then changes etc…
- Region above 8th somitomere never forms somites.
- Region above 8th is the head and neck.
- Thus below that is C1 Vertebra and down
What do somites become?
sclerotome and dermomyotome
Where is the sclerotome and what does it form?
The sclerotome is in the inner region of the somite.
Medial Scleretome forms:
Vertebral body
IV disk
Proximal ribs
Lateral Sceretome forms:
Vertebral arch
Pedicle of vertebra
Distal ribs
What are the sub-branches of the Dermomyotome?
Myotome
Dermatome
Where is the myotome and what does it form?
Myotome is in the middle of the somite
It forms the back muscles
Medial myotome (extensors) 1. Intrinsic back muscle
Lateral myotome (flexors)
- Limb muscles (after migration)
- Muscles of ventrolateral body wall
- Intrinsic back muscles
What does the lateral mesodermal plate give rise to?
Appendicular skeleton (arms and legs) Body wall musculature
Where does the axial skeleton come from?
The sclerotome
When to limbs become visible during development?
What initiates limb growth?
4th week
Growth is initiated by mesoderm
What is the relationship between the developing limb and dermatomes?
- Initial effect of limb growth on dermatomes modified by tissue reorganization
- Across the trunk = horizontal stripes, across arms = run lengthways
- Zones on the body extend out with developing limb bud; thus longitudinal axis of each limb
- Later undergo secondary modification, equivalent of folding -> complex final arrangement
What is the limb field?
- The limb field – initial growth depends on the limb field
- A patch of mesoderm per limb has capacity to form limb (“free limb”)
- Middle area forms limb, the area around forms flanking tissue eg. shoulder girdle
- Lots of redundancy -> remove free limb patch, surrounding cells can compensate
- BUT remove whole patch, no limb
- Transplant free limb patch and get ectopic limb
What is the relationship between limb development and the ectoderm?
- Limb development initiated by mesoderm but overlying ectoderm is critical in guiding the development (important in birth defects)
- Ectoderm is fragile outside layer ->minimum amount of damage before you perturb limb development (probably why limb disorders are frequent as a birth defect)
- Ectoderm overlying limb bud forms apical ectodermal ridge and now controls limb growth
- Splitting of ectodermal ridge results in diplopodia (result of damage to the tip of the limb)
How does normal digit development occur?
- feed and hands start of as symmetrical discs with digits sculpted by apoptosis
- syndactyly -> Can leave webbing behind, or failure can result in (fused fingers)
- Other mechanisms identify digits 1-5 (1 has 2 phalanges, other 3)
What do meromelia and amelia mean?
Meromelia • Absent Limbs Ameila • reduced limbs Can both be caused by thalidomide
What does the window of a teratogen mean/
- Each teratogen has window of opportunity to result in damage
- Very early on organ systems are set up.
- You will lose and organ depending on when you took the drug.
- For Thalidomide -> 20-36 days post conception was the window
What are the derivatives of the endoderm?
All derivatives are epithelial tissues • Epithelial lining of: • Gastrointestinal tract • Respiratory tracts • Tonsils • Thyroid • Parathyroid • Thymus • Liver • Pancreas In each case, forms organ along with mesodermal tissue
what is the ceolom?
cavity within which organs are suspended. It results from a 3D rolling and folding process. The embryo is a C-shaped tube.
How is the coelom formed?
First appears as split in lateral mesoderm and becomes continuous with extra embryonic space
Divides lateral mesoderm into splanchnic mesoderm (gut tube) below and somatic mesoderm (body wall) above
What gives rise to the body wall and viscera?
- Body Wall = Somatic mesoderm and ectoderm
come together in a bigger arch and enclose the gut tube; two wedges which were the ends of the somatic mesoderm come together and meet under the gut tube and seals - Gut Tube = Splanchnic mesoderm and endoderm formoming together in the midline underneath the embryo -> pinched off to form a tube and subsequent viscera
How does the coelom form?
Yolk sac separates from embryo with “purse string” [yolk sac = empty]
Space that becomes lumen of gut is pinched off
Lumen of gut remains initially continuous with yolk sac
Anterior end of space becomes foregut and posterior end hind gut
As the gut starts to form with splanchnic mesoderm (narrows left to right), it also narrows front to back -> enclosing lumen of the gut
Last part of the gut to be cut off is the mid-gut (foregut and hindgut are blind pocketings)
Eventually as purse string gets tighter and tighter a gut forms but still have opening through to the yolk sack -> maintained for some period of time
How does the oral cavity form?
- Prior to three weeks of age, no mouth or anus -> oral and anal pits present (stomadeum and procodeum)
- After 3 weeks of age, oral palate that separates foregut from stomadeum breaks, oral cavity forms
Oral cavity forms first (stomadeum opens first)
Ectoderm meets endoderm here -> if you break through the narrow opening there is ectoderm on outside meets endoderm on inside
If you follow surface from cheek -> mouth -> oral cavity pass from ectoderm (skin) to endodermal origin (inside the gut); boundary is at the back of your oral cavity
How does the anus and allantois form?
Development of anus (more complicated as there are 2 openings)
Anus sealed by cloacal membrane (ectoderm plus endoderm)
Cloacal Membrane seals the Allantois as Well.
Allantois stores nitrogenous waste in some species (vestigial in humans).
Between allantois and hind gut is urorectal septum (mesoderm)
Urorectal septum extends to divide rectum from urogenital tract
Grows back until it hits the Cloacal Membrane to divide to 2
openings;
1. Anus
2. Urogenital tract (remnant of Allantois).
The allantois forms the urinary bladder (which connects to the urethra)
what are the pharyngeal arches
Front end of animal there are embryonic gill like structures, the pharyngeal arches = endodermal lined expansions of the foregut -> gives rise to a number of structures
- The from 4 seperate pouches
what do each of the pharyngeal arches form?
Pharyngeal arch 1
• Eustachian tube (& external ear canal)
Pharyngeal arch 2
• Palatine tonsil
Pharyngeal arch 3
• Parathyroid (inferior)
• Thymus (epithelial part)
Pharyngeal arch 4
• Parathyroid (superior)
• Thymus
• Postbranchial bodies (parafollicular cells in thyroid)
Pharyngeal structures give rise to complex series of derivatives. Problem with formation of pharyngeal arches there is deficit in these symptoms
Where and from what does the heart form?
Myocardium (heart muscle) from lateral (splanchnic) mesoderm.
Forms below the gut.
How does the heart form?
What do the remnants of this process form?
2 endocardial Tubes brought together in Midline to form one tube.
The fusion produces the Heart
Remnants of tubes are:
- Aortic Arch Above
- Vena Cava vessels below
How does the heart get into its correct conformation?
- Folds to an S shape.
- Does this to form the 4 heart chambers.
- Other vessels into and out of the heart are from the Neural Crest
How common are congenital heart defects?
1:200
What is the most common congenital heart defect?
- Often of no consequence in fetus
- An issue immediately post-birth
- Commonest (25%) is ventricular septal defects
- Failure to divide single ventricle into left and right
what is a cause of atrial flow problems?
• Foramen Ovale does not close in the baby, as blood goes from Atria to Atria in babies.
• In a featus the Blood can only pass from RA to LA.
• Normally it should close, but it is patent in some conditions, and blood can flow between Atria
- Can also result from failure of the neural crest cells to migrate properly
What does the gut look like after 1 month of development?
At around one month, GIT consists of foregut and hindgut and a midgut still connected to the yolk sac by yolk stalk
What supplies the 3 regions of the gut?
Foregut supplied by coeliac a.
Midgut supplied by superior mesenteric a. Hindgut supplied by inferior mesenteric a.
How does the GIT develop in the early stages?
Initially GIT only as long as the foetus
• Quickly lengthens
• Begins to buckle in midgut around yolk stalk
• Rotates around axis of yolk stalk and superior mesenteric a.
• Folds large intestine across small intestine
• Further elongation of large intestine gives characteristic folding
What happens in week 6-7 of GIT development?
• Growing gut too big for body cavity (week 6-7) • Pushes into body stalk • By week 9, body cavity is bigger, gut retracts back
What is omphalocoele?
Failure of the gut to retract - it is usually fatal though it can be operated on in some cases
How common is Omphalocoele
1:25,000
How do the viscera develop?
• Trachea, lungs, liver and pancreas initially appear as endodermal out-pocketings • Endoderm in out-pocketings is interacting with mesoderm (chemical signals and layers of viscera)
What is situs invertus
• Body and organs are “mirror image” • Stomach on left, liver and lung lobes reversed, heart sounds reversed • No other deficit
How common it situs invertus?
1:10,000
Why does situs invertus occur?
Left right asymmetry is determined by the primitive groove.
Signals are distributed by the cilia which beat to generate currents right to left.
If the cilia are beating in the opposite direction or not at all it can cause situs invertus
What forms the urogenital system?
Apart from bladder and urethra, urogentital system is formed from intermediate mesoderm
• Urinary system forms first, then genital
What are the three kidney types which are produced?
1) Pronephros
2) Mesonephric tubules
3) Metanephros
What is the pronephros what does it become?
- Forms neprostomes and pronephric duct which extends down to the cloacus
- Nephrostomes degenerate, pronephric duct becomes mesonephris duct (with mesonephric tubules)
What are the mesonephric tubules?
- degenerates (leaving mesonephric duct)
- These ducts form the Vas Deferens
- Mullerian Duct - Doesn’t do anything in females
What is the metanephros?
Metanephros consists of kidney and ureters
• Ureters start off as budding from mesonephros at bladder
• Kidneys start low migrate to more superior position
What cell type forms the kidney and what induces its formation?
Kidney is from mesoderm not endoderm
Mesonephros induces metanephros
Is the initial development of the external genitalia different in males and females?
No
How does the penis form?
Penis forms by fusion of urogenital folds
What cuases a hypospadia?
- Urogenital folds should fuse completely to make urethra
- Partial fusion leaves urethral opening on base of penis - hypospadiasis
It can be corrected easily though surgery
Why is the first trimester important in terms of teratogens?
1) Most Organ Development occurs in early part of 1st Trimester ( 3 months).
2) Dangerous as Teratogens are exposed in this early stage.
3) Once Organs are laid down the rest is growth
4) First Trimester is most important.
