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Npr2 null mutants show initial overshooting followed by reduction of spiral ganglion axon projections combined with near-normal cochleotopic projection

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Abstract

Npr2 (natriuretic peptide receptor 2) affects bifurcation of neural crest or placode-derived afferents upon entering the brain stem/spinal cord, leading to a lack of either rostral or caudal branches. Previous work has shown that early embryonic growth of cochlear and vestibular afferents is equally affected in this mutant but later work on postnatal Npr2 point mutations suggested some additional effects on the topology of afferent projections and mild functional defects. Using multicolor lipophilic dye tracing, we show that absence of Npr2 has little to no effect on the initial patterning of inner ear afferents with respect to their dorsoventral cochleotopic-specific projections. However, in contrast to control animals, we found a variable degree of embryonic extension of auditory afferents beyond the boundaries of the anterior cochlear nucleus into the cerebellum that emanates only from apical spiral ganglion neurons. Such expansion has previously only been reported for Hox gene mutants and implies an unclear interaction of Hox codes with Npr2-mediated afferent projection patterning to define boundaries. Some vestibular ganglion neurons expand their projections to reach the cochlear apex and the cochlear nuclei, comparable to previous findings in Neurod1 mutant mice. Before birth, such expansions are reduced or lost leading to truncated projections to the anteroventral cochlear nucleus and expansion of low-frequency fibers of the apex to the posteroventral cochlear nucleus.

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Abbreviations

AC:

anterior canal crista

AVCN:

anteroventral cochlear nucleus

CB:

cerebellum

CN:

cochlear nucleus

CO:

cochlea

CoN:

cochlear nerve

CP:

choroid plexus

CVA:

cochleo-vestibular anastomosis

DCN:

dorsal cochlear nucleus

ED:

endolymphatic duct

FN:

facial nerve

FP:

floor plate

HC:

horizontal canal crista

MesV:

mesencephalic trigeminal projection

NG:

nodose ganglion

NVJ:

NeuroVue Jade

NVM:

NeuroVue Maroon

NVR:

NeuroVue Red

PC:

posterior canal crista

PG:

petrosal ganglion

PVCN:

posteroventral cochlear nucleus

r:

rhombomere

RB:

restiform body

S:

saccule

SG:

spiral ganglion

U:

utricle

VAS:

ventral acoustic stria

(a, p) VG:

(anterior, posterior) vestibular ganglion

VN:

vestibular nerve

V:

trigeminal ganglion

Vm:

trigeminal motor neurons

VIII:

octaval ganglion

VII:

facial (geniculate) ganglion

IX:

proximal glossopharyngeal ganglion

X:

proximal vagal ganglion

XI:

transient accessory ganglia

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Funding

This study was financially supported by the NIH (R01 AG060504 to BF) and by the Deutsche Forschungsgemeinschaft (Grant FOR 2060 project SCHM 2371/1 to HS).

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Authors and Affiliations

  1. Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany

    Hannes Schmidt

  2. Department of Biology & Department of Otolaryngology, CLAS, University of Iowa, 128 Jefferson Avenue, Iowa City, IA, 52242, USA

    Bernd Fritzsch

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  1. Hannes Schmidt
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Correspondence to Bernd Fritzsch.

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Schmidt, H., Fritzsch, B. Npr2 null mutants show initial overshooting followed by reduction of spiral ganglion axon projections combined with near-normal cochleotopic projection. Cell Tissue Res 378, 15–32 (2019). https://doi.org/10.1007/s00441-019-03050-6

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