Embryology 2

Question 1

What is a taratogen?

Answer 1

A factor ot agent that causes malformation of the embryo, may be physical, chemical or biological.

Question 2

When are embryos most vulnerable to teratogens?
Why?

Answer 2

In early embryological development, normally before 8 weeks.
This is because structures are less developed, division happens faster so malfunctions are more likely to be non-compatible with life.
The specific timing of vulnerability varies between different organs

Question 3

What time span are different organs more vulnerable to taratogens during development?

Answer 3

Heart - week 3 to 6
CNS - week 2 to 7
Limbs - week 3 to 6

Question 4

What is the most common cause of congenital abnormalities?

Answer 4

50% are unknown
25% are multifactorial
10% are chromosomal
8% is monogenic
7% is environmental

Question 5

What type of mutation in what area causes the most congenital abnormalities?

Answer 5

Single nucleotide substitutions in non-coding regulatory DNA is most associated with poor foetal development

Question 6

What is the prevalence of congenital abnormalities?

Answer 6

2.44% of pregnancies
1.8% of live births (diff due to abortion)
Most common are heart, urogenital, chromosomal and limb malformations.

Question 7

How does the mesoderm further develop after gestration?

Answer 7

After neural tube (ectoderm) formation the mesoderm is divided into different sections.
The chorda mesoderm
The paraaxial mesoderm
The intermediate mesoderm
The lateral plate mesoderm

Question 8

What are the important development paths from the mesoderm?

Answer 8

Lateral plate mesoderm
Splanchnic section
Circulatory system

Paraxial mesoderm
Somite mesoderm
Dermatome (including skeletal muscle), endotome, myotome, tendons and cartilage

Question 9

How does the heart tube develop?

Answer 9

The heart develops from the cranial aspect of the mesoderm splanchnic section of the lateral plate.
The endoderm secretes VEGFs causing the production of angioblasts (become blood vessels) and hematocysts (blood cells) in the mesoderm.
The mesoderm folds further so each side contains a paricardial cavity and a heart tube
The embryo then folds in a lateral direction and a cranial to caudal direction, this results in the fusion of the two heart tubes and pericardial cavities, the heart tube contained within the pericardial cavity. CC folding also moves the heart to a more central position
The dorsal mesoderm anchors the heart tube in place.

Question 10

What development happens to the heart tube after is has formed?

Answer 10

Endocardium and myocardium develop as layers around the heart tube.
heart tube is split into many sections
Aortic sac - becomes dorsal aorta
Truncus arteriosus - great arteries
Bubus cordix - conus arteriosus of the right ventricle and aortic vestibule of the left ventricle
Primitive ventricle - trabecular wall of ventricles
Primitive atria - pectinate muscle of atria
Sinus venosus - cornonary sinus and smooth wall of the right atrium

Question 11

How does the heart tube fold?

Answer 11

The truncus arteriosus and the bulbos cordis fold down and to the right
The primitive ventricle. primitive atria and sinus venosus fold up and to the left giving the characteristic heart shape

Question 12

How do the speta of the heart form?

Answer 12

The neural crest migratory cells contribute to septation.
The NCMC from the anterior cushion grows to become the septum intermediate between the primitive ventricle and primitive atria. from the strucutre the bicupsid and tricuspid valves can join.
The atrial septum develops from the spetum primum and septum secundum growing downwards to meet the septum intermediate
The ventricular muscle grows in size, some grows in an upwards direction to form the muscular part of the ventricular septum and is met by a membranous growth of the anterior cushion.

Question 13

What is the main cause of congenital heart defects?

Answer 13

Mainly related to transcription factor genes being non-functional.
This effects downstream signalling by (not) binding to promotors or enhancers.
Most problems occut during development

Question 14

Why is the lateral folding of the embryo important in limb development?

Answer 14

Results in an inner mesoderm layers and an outer ectoderm layer that can communicate by growth factors.

Question 15

What are the different limb axis?

Answer 15

In the hand - thumb is anterior, little finger is posterior, dorsal is dorsum and ventral is the palm
All limbs have a proximal and distal axis.

Question 16

What are the three different sections of limbs by development process?

Answer 16

The stylopod - humerus and femur
The zeugopod - the radius/ulnar and the tibia/fibular
The autopod - the digits and carpal bones

Question 17

How is the site of limb development determined?

Answer 17

Hox gene expression gradients and local retinoic acid signalling
Limb buds forms the apical ectodermal ridge.

Question 18

What causes limb buds to form?

Answer 18

Hox genes action the expression of Tbx and Pitx transcription factors, these regulate growth factors>
The apical ectodermal ridge signals FGF8 to the underlying lateral plate mesoderm, this becomes the limb bud mesoderm and produced FGF10.
In the ectoderm FGF10 activates Wnt signalling, resulting in more FGF8 production and stimulating outgrowth at the limb plates.

Question 19

What are the consequences of the removal of Tbx or Pitx genes?
What Tbx gene numbers are important?

Answer 19

Results in no limb development as no stimulation of FGF8 or FGF10 secretion. Shows in Holt-oram syndrome with no upper limb.
Tbx5 is associated with the upper limb
Tbx4 is associated with the lower limb

Question 20

What is the importance of limb patterning on the proximodistal axis?

Answer 20

Determins is stylopod, zeugopod or autopod.
Incorrect concentration of hox genes will result in the wrong bone strucutre during development.

Question 21

What is the importance of limb patterning on the anteroposterior axis?

Answer 21

Patterning is regulated by the zone of polarising activty which induces a posterior identity
Role in polyploidy

Question 22

How does the ZPA (zone of polarising activity) affect limb development?

Answer 22

Expresses the signalling molecules Shh (sonic hedgehof)

Question 23

What is the first wave of hox gene use in limb development.

Answer 23

HoxD genes are expressed.
Regulate the expression of ELCR Early Limb Control Region Genes and POST Posterior restriction expression, these encourage proximal limb and suppress distal limb development.

Question 24

What is the second wave of hox activity in limb development?

Answer 24

Expression of HoxD and Hoxb8 activates ZRS (ZPA regulatory sequuence), this enhances Shh expression
Shh activates Global Control Region GCR regulatory DNA which reverses the patttern of hox gene expression resulting in the development of the autopod along the posterior to anterior axis.

Question 25

How can polyplody be caused in a lab and naturally?

Answer 25

In a lab an additional ZPA at the anterior end causes additional little fingers after the thumb
Naturallt, a mutation is ZRS can result in additional fingers.

Question 26

What box genes are associated with what limb

Answer 26

Forelimb hox four and five
Hindlimb hox eight nine ten

Question 27

What limbs is Pitx1 associated with?

Answer 27

Hindlimb