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Review
. 2015 Feb;72(3):519-535.
doi: 10.1007/s00018-014-1759-0. Epub 2014 Oct 21.

The gene regulatory networks underlying formation of the auditory hindbrain

Marc A Willaredt  1 , Tina Schlüter  2 , Hans Gerd Nothwang  3   4
Affiliations
Review

The gene regulatory networks underlying formation of the auditory hindbrain

Marc A Willaredt et al. Cell Mol Life Sci. 2015 Feb.

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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Figures

Fig. 1
Fig. 1
Retinoic acid (RA) signaling prior rhombomeric boundary formation from E7.5 till E8.0. Dotted line with arrow indicates the synthesis of RA by RALDH2, whereas the dotted line with vertical bar illustrates the degradation of RA by Cyp26 proteins. Solid lines with arrows describe positive regulations. Anterior is to the right
Fig. 2
Fig. 2
Gene regulatory networks in r2. Expression pattern in r2 from E8.5 till E9.0 (a) and from E9.25 onwards (b). Arrows describe positive regulations, whereas vertical bars are standing for negative regulations. Dashed lines indicate indirect or not yet confirmed direct regulations. These genetic logics apply to all subsequent figures
Fig. 3
Fig. 3
Gene regulatory networks in r3, r5, and r6. a–c Expression patterns in r3 (a, b), r5 (c, d), and r6 (e, f) at E8.0–E8.5 (a, c, e) or from E8.5 onwards (b, d, f)
Fig. 4
Fig. 4
Gene regulatory networks in r4. Expression pattern in r4 at around E8.0 till E8.75 (a) or from E9.0 onwards (b)
Fig. 5
Fig. 5
Fgf3 subcircuit in different vertebrate species in the developing rhombencephalon. a zebrafish, b chicken, c mouse
See this image and copyright information in PMC

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