9. Development of the mouth, tongue and thyroid

Question 1

Where do neural crest cells migration from?

Answer 1

Diencephalon
Mesencephalon
Rhombomeres of the hindbrain

Question 2

Transcription factors determine expression patterns into the pharyngeal arches
under control of ______ signals

Answer 2

Transcription factors determine expression patterns into the pharyngeal arches
under control of endodermal signals

Question 3

Which CN is formed from the 1st pharyngeal arch?

Answer 3

Trigeminal (3 divisions, two to the first arch and one to the frontonasal prominence)

Question 4

Which CN is formed from the 2nd arch?

Answer 4

Facial

Question 5

Which CN is formed from the 3rd arch?

Answer 5

Glossopharyngeal

Question 6

Which CN is formed from the 4th and 6th arch?

Answer 6

Vagus
4th arch –> Superior laryngeal
6th arch –> Recurrent laryngeal

Question 7

bones are cartilage formed from the:
1st arch?
2nd arch?
3rd arch?
4th and 6th arch?

Answer 7

• 1st arch : mandible and middle ear. Malleus and Incus (all neural crest)
• 2nd arch : lesser horn and half body of hyoid, styloid ligament, styloid process, Stapes (all neural crest)
• 3rd arch : greater horn and half body hyoid (all neural crest)
• 4th and 6th : thyroid and cricoid (lateral plate mesoderm)

Question 8

What controls the mesenchyme in pharyngeal pouch formation?

Answer 8

HOX gene pattern in migrating crest cells

Question 9

What structure is the thyroid origin?

Answer 9

Foramen caecum

Question 10

Which swellings and arch form the tongue?

Answer 10

Swellings develop:

• 2 x lateral lingual (1st)
• Tuberculum impar (1st)
• Copula (3rd)
• Epiglottal (4th)

First arch forms the body of the tongue

Question 11

How does the terminal sulcus form?

Answer 11

When the thurd arch overgrows the second, the terminal sulcus becomes junction between 1st and 3rd arch mesenchyme

Question 12

What is the tongue innervation for the following:
General sensation?
Motor?
Taste?

Answer 12

General sensation:
Anterior 2/3 = Trigeminal (1st arch)
Posterior 1/3 = Glossopharyngeal (3rd arch)
Epiglottis/root= Superior laryngeal from the Vagus (4th arch)

Motor (to muscles):
Hypoglossal nerve

Taste:
Anterior 2/3 to facial nerve (as the 2nd pharnygeal arch)
Posterior 1/3 to the glossopharnygeal
Epiglottis to the Vagus

Question 13

Which nucleus of the brainstem shows somatotropy of the tongue?

Answer 13

The nucleus of tractus solitarius (NTS)

Question 14

Describe the course of thyroid formation from the foramen caecum?

Answer 14

1. Originates at the foramen caecum caudal to the tuberculum impar (foregut endoderm origin)
2. Migrates anterior to hyoid and thyroid cartilages (definitive position at week 7)
3. Track of migration marked by the thyroglossal duct (connects thyroid with tongue)

Question 15

What mutations are responsible for thyroid dysgenesis?

Answer 15

Mutations in transcription factors PAX8 and TITF1 (expressed as the bud descends)

Question 16

What are the cells involved in thyroid secretions?

Answer 16

Follicular cells: Secrete triiodothyronine and thyroxine

Parafollicular cells: Produce calcitonin (derived from the fourth pouch)

Question 17

What is a thyroglossal cyst?

Answer 17

Remnant of thyroglossal duct, mostly found in region of hyoid bone

Question 18

Clinical test for thyroglossal cyst

Answer 18

Moves upwards on tongue protrusion

Question 19

What are the 5 facial prominences that make up the face?

Answer 19

2 x maxillary prominences (V2)
2 x mandibular prominence (V3)
1 x frontonasal prominence (single structure, V1)

Question 20

What features and events lead to the formation of the face up to 10th week?

Answer 20

• Facial prominences from the 1st arch *
  All around the stomdeum
  Maxillary prominences grow towards the midline
  Medial and lateral nasal prominence surround the nasal pit
  Upper lip formed from maxillary prominences and fusion of the medial nasal prominences

Question 21

How is the palate formed from pharnygeal arches?

Answer 21

1.Maxillary processes (1st arch) on each side fusion in the midline, forming the intermaxillary segment. 
This gives rise to:
-Philtrum
-4 incisors
-Primary plate

2. The maxillary process forms the palatine shelf.
3. Palatine shelf flips above the tongue
4. Fusion in midline and with nasal septum.

Question 22

Result of abnormal fusion in palatine shelf?

Answer 22

Cleft lips and palate (can be bilateral or unilateral)

Question 23

What are the environmental causative factors associated with cleft lip/palate?

Answer 23

• Maternal age
• Medications antiepileptic agents or corticosteroids,
• Smoking
• Alcohol consumption during pregnancy
• Maternal illness was suggested to elevate the chance of CL/P
• Maternal diabetes
• Lack of dietary folic acid

Question 24

What are the genetic causative factors associated with cleft lip/palate?

Answer 24

• Aberrant gene variants are inherited from mother or father
• Inheritance is variable, often not strictly Mendelian probably because of environmental factors.

Question 25

Which gene mutations have been identified as causing cleft lip/palate?

Answer 25

PHF8 mutated

• in Siderius X-linked mental retardation
• Codes histone lysine demethylase.
• The oxygen dependence of lysine demethylase may explain increased incidence of CL/P under conditions of maternal hypoxia (e.g. smoking, hypertension, alcohol abuse)

IRF6 mutated
- in Van der Woude syndrome

IRF: interferon regulatory factor

Question 26

How is the IRF-6 network involved in craniofacial fects?

Answer 26

Network has many different parts that if mutated, result in clefting…

1. IRF-6 gene is upregulated by transcription factor p63. If mutated, CP forms.
2. Upstream IRF can upregulates Ripk4
3. Phosphorylated irf6 can upragulate Grhl3

Question 27

Effects of cleft lip and palate on individual?

Answer 27

• Difficulty feeding
• Hear problems, ear infections
• Speech problems
• Dental anomalies
• Social and psychological issues

Question 28

How is Cleft lip/palate corrected?

Answer 28

Surgery from 2-6 months

Requires further operations for speech and bone growth correction