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The gene regulatory networks underlying formation of the auditory hindbrain

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Abstract

Development and evolution of auditory hindbrain nuclei are two major unsolved issues in hearing research. Recent characterization of transgenic mice identified the rhombomeric origins of mammalian auditory nuclei and unraveled genes involved in their formation. Here, we provide an overview on these data by assembling them into rhombomere-specific gene regulatory networks (GRNs), as they underlie developmental and evolutionary processes. To explore evolutionary mechanisms, we compare the GRNs operating in the mammalian auditory hindbrain with data available from the inner ear and other vertebrate groups. Finally, we propose that the availability of genomic sequences from all major vertebrate taxa and novel genetic techniques for non-model organisms provide an unprecedented opportunity to investigate development and evolution of the auditory hindbrain by comparative molecular approaches. The dissection of the molecular mechanisms leading to auditory structures will also provide an important framework for auditory processing disorders, a clinical problem difficult to tackle so far. These data will, therefore, foster basic and clinical hearing research alike.

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Abbreviations

A–P:

Anterior–posterior

AVCN:

Anterior ventral cochlear nucleus

BMP:

Bone morphogenetic protein

CNC:

Cochlear nucleus complex

DCN:

Dorsal cochlear nucleus

E:

Embryonic

LSO:

Lateral superior olive

MNTB:

Medial nucleus of the trapezoid body

NA:

Nucleus angularis

NL:

Nucleus laminaris

NLL:

Nucleus of the lateral lemniscus

NM:

Nucleus magnocellularis

P:

Postnatal

PVCN:

Posterior ventral cochlear nucleus

r:

Rhombomere

RA:

Retinoic acid

SOC:

Superior olivary complex

TF:

Transcription factor

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Acknowledgments

We thank Geoff Manley for helpful discussions and input to this paper. We also acknowledge insightful comments from two anonymous reviewers. M.A. Willaredt is financed by the Cluster of Excellence Hearing4all, and T. Schlüter by the Research Training Group Molecular Basis of Sensory Biology GRK 1885/1.

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  1. Neurogenetics group, Center of Excellence Hearing4All, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26111, Oldenburg, Germany

    Marc A. Willaredt, Tina Schlüter & Hans Gerd Nothwang

  2. Research Center for Neurosensory Science, Carl von Ossietzky University Oldenburg, 26111, Oldenburg, Germany

    Hans Gerd Nothwang

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Willaredt, M.A., Schlüter, T. & Nothwang, H.G. The gene regulatory networks underlying formation of the auditory hindbrain. Cell. Mol. Life Sci. 72, 519–535 (2015). https://doi.org/10.1007/s00018-014-1759-0

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  • DOI: https://doi.org/10.1007/s00018-014-1759-0

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