HOX TfS

Question 1

What are homoeotic (hox) genes?

Answer 1

• set of genes that control the body plan of an embryo along the anterior-posterior axis during the early stages of development
• determine where specific body parts and structures will form

Question 2

What is a typical homeodomain protein?

Answer 2

• encoded by Hox genes
• helix-turn-helix motif allows DNA binding
• binds ATTA sequences
• act as transcriptional regulators involved in the development of body parts and structures

Question 3

What are hox clusters?

Answer 3

• clusters of Hox genes found in complex vertebrates
• HOXA, HOB, HOC etc
• the order in which the Hox complex is sequence is in line with the segments of the hind brain and spinal cord i.e. the hox genes are in the order they develop in

Question 4

What can ectopic expression of Hox genes do?

Answer 4

• abnormalities in bone formation
• e.g. ectopic expression of Hoxa7 in mice leads to homeotic transformations of vertebra such as missing or extra ribs or vertebra in the wrong order

Question 5

What can hox gene loss of function / KO mutations do?

Answer 5

• Hoxa3 KO in mice leads to severe head and neck abnormalities
• others lead to regional bone abnormalities, missing bones and ribs or severe kidney defects

Question 6

Describe two naturally occurring Hox mutations seen in humans

Answer 6

• HOXD13 gain of function leads to digit webbing and duplications
• HOXA13 leads to hand-foot-genitcal syndrome

Question 7

When can hox genes be seen in cancer?

Answer 7

• HOXA5 regulates p53
• hypermethylation is seen in breast cancer
• other examples of HOX promoter methylation are seen in other cancers such as lung cancer

Question 8

What are pax genes?

Answer 8

• another set of genes involved in development
• development of specific tissues and organs
• not arranged in clusters
• paired domain + homeodomain bind DNA

Question 9

What do pax and hox stand for?

Answer 9

• paired box
• homeobox

Question 10

How are human PAX genes organised?

Answer 10

• grouped by the presence of domains
• all have paired domain
• some then also have:
• homeodomain or octapeptide
• 4 groups

Question 11

What are some PAX mutations seen in humans?

Answer 11

PAX8 seen in follicular thyroid tumours
PAX5 seen in non-hodgins lymphomas

Question 12

Which region is PAX6 responsible for in development? How do we know?

Answer 12

• the eye
• human mutations lead to iris absence
• ectopic pax6 expression in drosophila results in eye-like structures being formed where they shouldnt be

Question 13

What are pou genes?

Answer 13

• also involved in development
• no common pattern
• encode proteins such as:
• oct4 in ESC + oocytes
• RPF1which is commonly seen mutated in Wilms tumour

Question 14

What is the role of Pou gene product Oct4?

Answer 14

• maintains stem cell identity
• declines during differentiation and HOXA5 increases

Question 15

Why are fruit flies good for studying development?

Answer 15

• small
• short generation time 9 days
• genome small and easy to map
• quick generation time
• segmented pattern of gene expression with classes of genes that define segments - drosophila homoeotic genes

Question 16

What was the first example of a homeobox gene?

Answer 16

• inappropriate expression of the antennapedia gene causes the formation of legs rather than anttanae
• turned out to be a homoeotic gene
• high conserved sequence known as the homeodomain found in all hox genes