© Springer Nature Singapore Pte Ltd. 2017 57
T. Tsuji (ed.), Organ Regeneration Based on Developmental Biology,
DOI 10.1007/978-981-10-3768-9_4
Chapter 4
Inner Ear Organoids: Recapitulating Inner
Ear Development in 3D Culture
Alhasan N. Elghouche, Rick F. Nelson, and Eri Hashino
Abstract The inner ear contains sensory epithelia composed of mechanosensitive
hair cells, supporting cells, and sensory neurons that work in concert to detect sound
and positional information and transmit those signals to the brain. Within the back-
drop of embryogenesis, inner ear development follows an intricate pathway of sig-
naling cues and morphological changes, leading to its complex final three-dimensional
(3D) structure. Application of various small molecules and recombinant proteins to
mouse embryonic stem cells at specific time points in vitro has enabled recapitula-
tion of developmental cues with subsequent formation of inner ear organoids. This
has resulted in a model system of inner ear development that is easily derived,
manipulated, and analyzed. These organoids contain functional mechanosensitive
hair cells, supporting cells, and sensory neurons, which phenocopy functional com-
ponents of the inner ear responsible for detection of positional information. The
potential applications of this system include investigation of inner ear development,
disease modeling, drug screening, and therapy development. This chapter highlights
the process of in vivo inner ear development, the rationale and process behind inner
ear organoid formation, and potential applications and limitations of this in vitro
model system.
Keywords Inner ear • Hearing • Balance • Embryonic development • Stem cells •
3D culture • Organogenesis
4.1 Introduction
The mammalian inner ear is a complex, labyrinthine structure containing two sen-
sory organs—the cochlea and the vestibular apparatus. The cochlea detects sound
with the auditory sensory epithelium in the organ of Corti, whereas the vestibular
apparatus detects positional information with sensory epithelia in the cristae of the
A.N. Elghouche • R.F. Nelson • E. Hashino (*)
Department of Otolaryngology-Head & Neck Surgery, Indiana University School of
Medicine, Indianapolis, IN 46202, USA
e-mail: [email protected]