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Smoothened overexpression causes trochlear motoneurons to reroute and innervate ipsilateral eyes

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Abstract

The trochlear projection is unique among the cranial nerves in that it exits the midbrain dorsally to innervate the contralateral superior oblique muscle in all vertebrates. Trochlear as well as oculomotor motoneurons uniquely depend upon Phox2a and Wnt1, both of which are downstream of Lmx1b, though why trochlear motoneurons display such unusual projections is not fully known. We used Pax2-cre to drive expression of ectopically activated Smoothened (SmoM2) dorsally in the midbrain and anterior hindbrain. We documented the expansion of oculomotor and trochlear motoneurons using Phox2a as a specific marker at E9.5. We show that the initial expansion follows a demise of these neurons by E14.5. Furthermore, SmoM2 expression leads to a ventral exit and ipsilateral projection of trochlear motoneurons. We compare that data with Unc5c mutants that shows a variable ipsilateral number of trochlear fibers that exit dorsal. Our data suggest that Shh signaling is involved in trochlear motoneuron projections and that the deflected trochlear projections after SmoM2 expression is likely due to the dorsal expression of Gli1, which impedes the normal dorsal trajectory of these neurons.

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Acknowledgments

We would like to thank Drs. T. Ohyama and A. Groves for providing the Pax2-cre mice, Dr. Susan L Ackerman for providing the Unc5c mutant mice, Dr. David H Rowitch for giving us the SmoM2 construct, Dr. J-F. Brunet for the Phox2a probe, and Dr. A. McMahon for the Gli1 probe. We appreciate the collaboration with Dr. Ning Pan on this project.

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  1. Department of Biology, University of Iowa, Iowa City, IA, 52242, USA

    Israt Jahan, Jennifer Kersigo, Karen L. Elliott & Bernd Fritzsch

  2. Department of Otolaryngology, University of Iowa, Iowa City, IA, 52242, USA

    Bernd Fritzsch

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  1. Israt Jahan
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Correspondence to Bernd Fritzsch.

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Jahan, I., Kersigo, J., Elliott, K.L. et al. Smoothened overexpression causes trochlear motoneurons to reroute and innervate ipsilateral eyes. Cell Tissue Res 384, 59–72 (2021). https://doi.org/10.1007/s00441-020-03352-0

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