1. Development of the auditory system
Dr. Nandor Nagy
Semmelweis University, Budapest 1

3. Fig. 1 Development of cranial placodes in vertebrates (modified from Schlosser and Northcutt 2000; Schlosser 2006). ...
Fig. 1 Development of cranial placodes in vertebrates (modified from Schlosser and Northcutt 2000; Schlosser 2006). (A) Six1, Six4, and Eya1 define the preplacodal ectoderm (red), located adjacent to the neural plate (grey) and the neural crest (blue) as here shown for a neural plate stage Xenopus embryo. The preplacodal ectoderm serves as a common primordium for all placodes. Although no fate map is available for Xenopus, expression patterns of several transcription factors (colored lines) suggest that the different placodes arise approximately from the regions indicated by white letters. (B) Cranial placodes in a tailbud stage Xenopus embryo. (C) Six1 is first expressed in the preplacodal ectoderm. (D) At tailbud stages, Six1 expression continues in all placodes. The asterisks indicate the position of the fused profundal and trigeminal ganglia (the respective placodes are already disappearing at this stage). (E) Summary of tissues and signals involved in induction of panplacodal primordium (right half, red arrows, and bars) and neural crest (left half, blue arrows, and bars) from the perspective of the binary competence model. According to this model, competence for placode induction is confined to non-neural ectoderm (light yellow), whereas competence for neural crest induction is confined to neural ectoderm (light green). Activating signals are denoted by arrows, inhibitory signals by bars. For details, see text and Schlosser (2006). Ad = adenohypophyseal placode; Ol = olfactory placode; L = lens placode; V: trigeminal placode/ganglion; Pr = profundal placode/ganglion, LL = lateral line placodes; EB = epibranchial placodes, Ot = otic placode.
Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please
Integrative and Comparative Biology, Volume 47, Issue 3, 22 May 2007, Pages 343–359,
The content of this slide may be subject to copyright: please see the slide notes for details. 3

5. In humans, mutations in SIX1 are causative in some individuals afflicted with Branchio-otic Syndrome (specifically BOS3). These patients have minor craniofacial defects and profound hearing loss, presumably due to defects in otic placode/inner ear development
Zheng, W. et al. Development 2003;130: 5

7. Development of Inner Ear
-all of the inner ear derivatives arise from ectoderm
The otic pit forms as this thickened (placodal) ectoderm invaginates 26 E

8. (A)
(B)
9 day mouse
The neural tube in the region of the hindbrain induces formation of the otic placode (A) and then otic vesicle (B), dorsolateral to the pharynx
The otic placode invaginates to form an otic pit and finally the otic vesicle. Its surface aspect is dorsal to the 2nd branchial cleft

9. The otic pit deepens and pinches off from the surface.
The otic pit is located dorsal to the second pharyngeal cleft.

11. Differentiation of the otic vesicle yields three major subdivisions of the inner ear: the endolymphatic sac and duct and the utricular and saccular portions.
-approx. Human Age: 36 days

12. Malformations of inner ear:
-a syndrome characterized by vestibulocochlear dysplasias is CHARGE syndrome (coloboma of the eye, heart defects, atresia of the choanae, retarded growth and development, genital and urinary anomalies, and ear anomalies and hearing loss), often caused by mutations in CHD7
-Conditions such as rubella can lead to maldevelopment of the organ of Corti, causing inner ear deafness

13. Morphogenesis of the mouse inner ear over a 7-day period in embryogenesis,
revealed by filling the cavity of the developing otocyst with opaque paint.

14. An outgrowth of the saccule forms the cochlear duct.
9th week of embryogenesis
The tall, columnar epithelial cells of the growing cochlear duct become the Organ of Corti (the hearing receptors).

16. Hearing loss can result from mutations of the many different genes expressed in the inner ear.

17. Embryonic Development of the Ear
Begins in the fourth week of development
The inner ear forms from ectoderm
The middle ear forms from the first pharyngeal pouches (endoderm)
Ear ossicles develop from cartilage (neural crest)
The external ear differentiates from the first branchial groove (ectoderm)
Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

18. Development of Middle Ear
The bones of the middle ear are derived from the cartilage (cranial neural crest derivatives) of the first and second arch.

19. Cranial neural crest cell migration in the mammalian head (mesenchymal cells)
devbio8e-fig jpg

20. Hoxa2 mutation

21. As the inner ear differentiates, the middle ear forms
As the inner ear differentiates, the middle ear forms. The endoderm of the first pharyngeal pouch will line the middle ear cavity and auditory tube.

22. The pharyngeal pouches contain the primordia of a number of different adult structures

23. Brachial pouches: outpocketings of pharynx endoderm

24. Development of external ear
1st pharyngeal
cleft
The external ear also forms from tissues of the first and second pharyngeal arches.
hillock #1 forms the tragus and hillock #6 forms the antiragus, as well as part of the helix

25. Anomalies of the external ear: microtia (small auricle; Fig
Anomalies of the external ear: microtia (small auricle; Fig. A, B) or anotia (absence of the auricle (Fig C)
Fig. D and F: external ear of a boy with BOR syndrome. The upper arrow indicates a preauricular pit and the lower arrow indicates a cervical fistula

26. -branchio-oto-renal (BOR) syndrome (mutation in the EYA1 gene).
-the cup-shaped ears and branchial cysts (arrow). Preauricular pits and tags sometimes accompany the syndrome
-also known as Melnick-Frasier syndrome, BOR is most often caused by mutations in the EYES ABSENT HOMOLOG 1 (EYA1) gene. As the name suggests, mutations in the Drosophila homolog of this gene (Eya) affect the eyes