Development of palate

Question 1

Palate formation timeline

Answer 1

week 6-12

Question 2

Purpose of the primary palate

Answer 2

Demarcates the oral vs nasal components, derived from fused medial nasal prominences (part of frontonasal prominence) - intermaxillary segment

Question 3

How does bone of the primary palate initially get laid down?

Answer 3

intramembranous ossification

Question 4

Role of the definitive (secondary) palate

Answer 4

1. separates the nasal airway and oral cavity
2. Important for: mastication, sensation, speech

Question 5

How do palatal shelves elevate?

Answer 5

1. Forces extrinsic to the palate (involving the tongue)
2. Intrinsic forces generated within the palate

Question 6

Why might the tongue withdraw due to extrinsic forces?

Answer 6

Head lifting from cardiac plate
Meckel’s cartilage growth
Increased height of nasal cavity

Does this cause or facilitate elevation? … more research required….

Question 7

What intrinsic force might cause the palatal shelves to elevate?

Answer 7

1. Hydration of extracellular matrix (hyaluronan or GAG) binds 10x its weight in water (turgidity). There is evidence that hyaluronan accumulates prior to elevation - further evidence for this theory.
2. Mesenchymal cells: appear to shorten by contractile microfilaments.
3. Forces directed via collagen fibres (unlikely though)
4. Altered blood flow?

MOST likely a combination of all the above factors

Question 8

How could gender impact palatal shelf elevation?

Answer 8

Males might elevate earlier (during week 7)

Females later (week 8)

Question 9

How do the shelves grow towards each other?

Answer 9

Mesenchymal cells migrating in and extra cellular matrix being laid down.

Question 10

What is are the cells in between the two shelves known as?

Answer 10

Midline epithelial cells

Question 11

Epithelial adhesion

Answer 11

Prevents fusion to the incorrect structures (i.e. the tongue)

This is a result of specific sticky surface glycoproteins.

Question 12

Three theories of palatal fusion (how does the midline epithelial cells disintegrate/disappear?)

Answer 12

1. Epithelial-mesenchymal transition
2. Apoptosis of epithelial cells
3. Migration to the nasal or oral edge

Question 13

Fusion problems

Answer 13

1. Failure of fusion: cleft palates (completely or incompletely)
2. Epithelial remnants: epithelial cells that do not migrate or die causing epithelial cell rests (cystic potential - pain in the roof of the mouth).

Question 14

Cleft palate: gender?

Answer 14

more common in women

Question 15

Cleft palate - aetiology

Answer 15

20% - monogenic (inherited)
5% - teratogens (alcohol)
1% - chromosomal abnormalities
20% - unknown aetiology

Question 16

Cleft palate: risk factors

Answer 16

Smoking, alcohol abuse, drugs-both medical and recreactional, viruses, rubella, too much vitamin A (or other retinoids, deficiencies in folic acid.

Question 17

Hyaluronan made by…

Answer 17

enzymes HA synthase 1, 2 and 3

Question 18

HA sizes

Answer 18

HA synthase 1 and 2 larger molecular weight (2 million Da)
HA synthase 3 (20000 Da)

Question 19

HA types distribution

Answer 19

Early: in the head region, mainly HA synthase 2.

As neural crest cells migrate in, HA synthase 1 and 3 increasing.

Branchial arches: HA synthase 2.

Question 20

Knockout mouse

Answer 20

“silencing” a specific gene and seeing the effect of this on development.

Question 21

How have knockout mice demonstrated a need for a particular growth factor in palate development?

Answer 21

TGFbeta3 knockout mouse led to a cleft palate