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Question 1

What is the rate of children born a ‘birth defect’?

Answer 1

1:33 babies have a “birth defect” which must be treated/managed
(this is live births only- many more case miscarriage)

Question 2

What is hypospadia?

Answer 2

A misplaced urethral opening in males

Question 3

Where does fertilization occur in the FT?

Answer 3

The most distal region

Question 4

What are the 5 stages of embryonic development

Answer 4

1. Early Blastocyst Formation
2. Blastocyst Split
3. Two Germ layer Stage
4. Three Germ Layer Stage
5. Extra-embryonic tissue

Question 5

What occurs during early blastocyst development?

Answer 5

• 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’

Question 6

What are the two types of cell in the blastocyst?

Answer 6

Outer epithelial layer (trophoblast)
- Forms extra embryonic structures like placenta.
Inner cell mass
- Forms embryo

Question 7

At what stage of development does the blastocyst implant into the uterine wall?

Answer 7

Between days 5 and 10

Question 8

What happens during the two germ layer stage?

Answer 8

• 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

Question 9

What does the hypoblast from?

Answer 9

It bgins to surround the blastocoele - it is called the yolk sac though it does not have any yolk in humans

Question 10

What does the epiblast form?

Answer 10

• 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

Question 11

What are three germ layers and what do they form?

Answer 11

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

Question 12

How does the Notochord form and what does it do?

Answer 12

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.

Question 13

What is the neural crest?

Answer 13

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

Question 14

What are the neural crest derivatives and what happens if these cell fail to migrate properly?

Answer 14

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

Question 15

What is the difference between mesoderm and mesenchyme?

Answer 15

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)

Question 16

What are the three types of mesoderm?

Answer 16

1) Paraxial
2) Intermediate
3) Lateral

Question 17

What does paraxial mesoderm from?

Answer 17

Closest to Midline

(i) Dermis of skin
(ii) Axial skeleton
(iii) Axial and limb buds

Question 18

What does intermediate mesoderm from?

Answer 18

In Between

• Urogenital system (kidneys + tubes)

Question 19

What does lateral mesoderm from?

Answer 19

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

Question 20

What are somites and how do they form?

Answer 20

• 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.

Question 21

What happens to the somitomeres above and below 8?

Answer 21

• 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

Question 22

What do somites become?

Answer 22

sclerotome and dermomyotome

Question 23

Where is the sclerotome and what does it form?

Answer 23

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

Question 24

What are the sub-branches of the Dermomyotome?

Answer 24

Myotome

Dermatome

Question 25

Where is the myotome and what does it form?

Answer 25

Myotome is in the middle of the somite It forms the back muscles ``` Medial myotome (extensors) 1.  Intrinsic back muscle ``` Lateral myotome (flexors) 1.   Limb muscles (after migration) 2.   Muscles of ventrolateral body wall 3.   Intrinsic back muscles

Question 26

What does the lateral mesodermal plate give rise to?

Answer 26

``` Appendicular skeleton (arms and legs) Body wall musculature ```

Question 27

Where does the axial skeleton come from?

Answer 27

The sclerotome

Question 28

When to limbs become visible during development? | What initiates limb growth?

Answer 28

4th week | Growth is initiated by mesoderm

Question 29

What is the relationship between the developing limb and dermatomes?

Answer 29

* 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

Question 30

What is the limb field?

Answer 30

* 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

Question 31

What is the relationship between limb development and the ectoderm?

Answer 31

* 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)

Question 32

How does normal digit development occur?

Answer 32

* 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)

Question 33

What do meromelia and amelia mean?

Answer 33

``` Meromelia • Absent Limbs Ameila • reduced limbs Can both be caused by thalidomide ```

Question 34

What does the window of a teratogen mean/

Answer 34

* 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

Question 35

What are the derivatives of the endoderm?

Answer 35

``` 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 ```

Question 36

what is the ceolom?

Answer 36

cavity within which organs are suspended. It results from a 3D rolling and folding process. The embryo is a C-shaped tube.

Question 37

How is the coelom formed?

Answer 37

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

Question 38

What gives rise to the body wall and viscera?

Answer 38

1. 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 2. Gut Tube = Splanchnic mesoderm and endoderm formoming together in the midline underneath the embryo -> pinched off to form a tube and subsequent viscera

Question 39

How does the coelom form?

Answer 39

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

Question 40

How does the oral cavity form?

Answer 40

* 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

Question 41

How does the anus and allantois form?

Answer 41

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)

Question 42

what are the pharyngeal arches

Answer 42

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

Question 43

what do each of the pharyngeal arches form?

Answer 43

  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

Question 44

Where and from what does the heart form?

Answer 44

Myocardium (heart muscle) from lateral (splanchnic) mesoderm. Forms below the gut.

Question 45

How does the heart form? | What do the remnants of this process form?

Answer 45

2 endocardial Tubes brought together in Midline to form one tube. The fusion produces the Heart Remnants of tubes are: 1. Aortic Arch Above 2. Vena Cava vessels below

Question 46

How does the heart get into its correct conformation?

Answer 46

* 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

Question 47

How common are congenital heart defects?

Answer 47

1:200

Question 48

What is the most common congenital heart defect?

Answer 48

*   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

Question 49

what is a cause of atrial flow problems?

Answer 49

• 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

Question 50

What does the gut look like after 1 month of development?

Answer 50

At around one month, GIT consists of foregut and hindgut and a midgut still connected to the yolk sac by yolk stalk

Question 51

What supplies the 3 regions of the gut?

Answer 51

Foregut supplied by coeliac a. | Midgut supplied by superior mesenteric a. Hindgut supplied by inferior mesenteric a.

Question 52

How does the GIT develop in the early stages?

Answer 52

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

Question 53

What happens in week 6-7 of GIT development?

Answer 53

•  Growing gut too big for body cavity (week 6-7) •  Pushes into body stalk •  By week 9, body cavity is bigger, gut retracts back

Question 54

What is omphalocoele?

Answer 54

Failure of the gut to retract - it is usually fatal though it can be operated on in some cases

Question 55

How common is Omphalocoele

Answer 55

1:25,000

Question 56

How do the viscera develop?

Answer 56

•  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)

Question 57

What is situs invertus

Answer 57

•  Body and organs are “mirror image” •  Stomach on left, liver and lung lobes reversed, heart sounds reversed •  No other deficit

Question 58

How common it situs invertus?

Answer 58

1:10,000

Question 59

Why does situs invertus occur?

Answer 59

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

Question 60

What forms the urogenital system?

Answer 60

Apart from bladder and urethra, urogentital system is formed from intermediate mesoderm •  Urinary system forms first, then genital

Question 61

What are the three kidney types which are produced?

Answer 61

1) Pronephros 2) Mesonephric tubules 3) Metanephros

Question 62

What is the pronephros what does it become?

Answer 62

* Forms neprostomes and pronephric duct which extends down to the cloacus * Nephrostomes degenerate, pronephric duct becomes mesonephris duct (with mesonephric tubules)

Question 63

What are the mesonephric tubules?

Answer 63

* degenerates (leaving mesonephric duct) * These ducts form the Vas Deferens * Mullerian Duct - Doesn’t do anything in females

Question 64

What is the metanephros?

Answer 64

Metanephros consists of kidney and ureters •  Ureters start off as budding from mesonephros at bladder •  Kidneys start low migrate to more superior position

Question 65

What cell type forms the kidney and what induces its formation?

Answer 65

Kidney is from mesoderm not endoderm | Mesonephros induces metanephros

Question 66

Is the initial development of the external genitalia different in males and females?

Answer 66

No

Question 67

How does the penis form?

Answer 67

Penis forms by fusion of urogenital folds

Question 68

What cuases a hypospadia?

Answer 68

*   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

Question 69

Why is the first trimester important in terms of teratogens?

Answer 69

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.