Early development of the cochlea of the common marmoset, a non-human primate model

Abstract

Background Fine-tuned cochlear development is essential for hearing. Owing to the difficulty in using early human fetal samples, most of our knowledge regarding cochlear development has been obtained from rodents. However, several inter-species differences in cochlear development between rodents and humans have been reported. To bridge these differences, we investigated early otic development of a non-human primate model animal, the common marmoset (Callithrix jacchus). Methods We examined 20 genes involved in early cochlear development and described the critical developmental steps for morphogenesis, which have been reported to vary between rodents and marmosets. Results The results revealed that several critical genes involved in prosensory epithelium specifications showed higher inter-species differences, suggesting that the molecular process for hair cell lineage acquisition in primates differs considerably from that of rodents. We also observed that the tempo of cochlear development was three times slower in the primate than in rodents. Conclusions Our data provide new insights into early cochlear development in primates and humans and imply that the procedures used for manipulating rodent cochlear sensory cells cannot be directly used for the research of primate cells due to the intrinsic inter-species differences in the cell fate determination program.

Development of the stria vascularis in the common marmoset, a primate model

“…First, we examined the E87 cochlea, in which hair cell differentiation has been observed in the sensory epithelium of the basal turns and not in the apical turns 6 . In the E87 cochlea, ATP1A1 expression was observed throughout the cochlear epithelium.…”

“…in cochlear development in rodents and humans have been reported 1 . To overcome this limitation in sampling and to minimize species differences, the common marmoset (Callithrix jacchus), a small primate model, has been used in this study to understand cochlear development [4][5][6] , as well as genetic or age-related hearing loss 7 . A similar approach has been adopted in research on the central nervous system 8 .…”

“…A similar approach has been adopted in research on the central nervous system 8 . We have previously reported on cochlear development in the common marmoset, including its basic anatomical staging compared to humans and mice, as well as the expression patterns observed in conventional markers of hair cells, supporting cells, spiral ganglion neurons, and other cochlear cells [4][5][6] . Furthermore, we revealed several differences in the development of hair cells and spiral ganglion neurons between rodents and marmosets, and demonstrated the similarity to the development process in humans 4,5 .…”

Induced Pluripotent Stem Cells, a Stepping Stone to In Vitro Human Models of Hearing Loss

“…Nonetheless, there are important differences between humans and mice that affect the potential of these latter to serve as models for HL in man [ 86 ]; they present a shorter lifespan that may preclude them from appropriately modelling the late onset and progressive HL recorded in many patients, as well as a lack of genetic heterogeneity that is in stark contrast to that found in human populations [ 1 , 87 ]; they also differ in the time that is required for their inner ears to fully develop and in the amino acid sequence of important proteins [ 88 ]. Moreover, there are mouse lines that, despite carrying genetic mutations identical to some found in patients, do not exhibit the same symptoms [ 9 , 10 , 87 ]; in this regard, differences in gene expression patterns between primates and rodents have been associated with a failure of some of the murine models to recapitulate the human disease [ 9 , 21 , 24 , 25 , 26 ]. The common marmoset, also amenable to genetic modification, has thus been proposed as a more predictive model of human cochlear development and pathology [ 21 , 22 ].…”

“…Many studies are now being conducted on zebrafish, a model that can also undergo genetic modifications and that offers several other advantages, such as a much faster life cycle than that of the mouse and the generation of very large numbers of test organisms that are transparent at their early developmental stages, greatly facilitating their analysis and making the model amenable to high-throughput screenings [ 14 , 15 , 16 ]; nonetheless, the results obtained on this model must be validated on some mammalian system [ 17 , 18 , 19 ]. A critical shortcoming to all these models is that none of them are of human origin and inter-species differences may be expected [ 7 , 20 ]; in this regard, highly relevant data are being obtained from studies on the common marmoset, a non-human primate model of cochlear development and genetic HL [ 21 , 22 , 23 , 24 ]. There are strong indications that the common marmoset may constitute a more predictive model than the mouse since the time course for cochlear development in the former is much longer than in the latter and may thus more closely resemble the human process.…”