Organogenesis (limb development)

Question 1

AER = apical ectodermal ridge

Answer 1

a structure that forms from the ectodermal cells at the distal end of each limb bud and acts as a major signalling centre to ensure proper development of a limb
It goes along the dorsal-ventral boundary between the dorsalventral ectoderm.

Question 2

limb bud

Answer 2

a structure formed early in vertebrate limb development. As a result of interactions between the ectoderm and underlying mesoderm, formation occurs roughly around the fourth week of development.

Question 3

Two major types of limb bud

Answer 3

• Outer layer of ectodermal epithelial cells (at the tip of the limb bud, apical ectodermal ridge)
• Mesenchymal cells (undifferentiated, proliferating cells that can differentiate into other types of cells, they can renew themselves)

Question 4

describe the correlation between FGF signalling and AER with limb growth

Answer 4

They are essential for limb growth
- remove AER at early: most of limbs missing
- remove AER at later stage: loss of the ends of the digits
-remove AER but apply FGF signals at the outside of the limb bud: limb can develop quite normally

Question 5

ZPA (Zone of polarizing activity)

Answer 5

The organizing region for antero-posterior axis = the polarizing region or zone of polarizing activity

Question 6

Morphogen

Answer 6

molecules whose spatial concentration varies to specify cell fate and patterning depending on the different concentrations.

Question 7

most important signalling in ZPA?

Answer 7

sonic hedgehog (Shh) expressed in the posterior region of normal limb bud (ZPA)

Question 8

absence and presence of SHH signalling, explain the pathway with the Gli transcription factor.

Answer 8

Absence of SHH: Gli as a repressor: Patched
(SHH receptor) will not be internalised into the cytoplasm. Gli (transcription factor) can respond to patched. Gli transcription factors will stay phosphorylated and move into the nucleus where they function as repressors. Gli is transcriptionally repressing gene expression
Presence of SHH: Gli as an activator: Patched receptor is internalized and Gli will be dephosphorylated and Gli moves into nucleus as activator. This way Gli can activate transcription.

Question 9

explain Gli transcription factor

Answer 9

Gli transcription factors are known to be involved in limb development. If mutations occur in transcription factors, it will give rise to limb malformations. The phenotype is polysyndactyly: missing digits or having more digits.

Question 10

Hox genes in limb development

Answer 10

Hox genes are expressed during limb
development: early hox genes, more proximal, late hox genes, more
distal.

Question 11

p63 in limb development

Answer 11

p63 mutations give rise to ectrodactyly: p63 is expressed in AER