Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers

0541345 - BTÚ 2021 RIV US eng J - Článek v odborném periodiku
Filova, Iva - Dvořáková, Martina - Bohuslavová, Romana - Pavlínek, Adam - Elliott, K. L. - Vochyánová, Simona - Fritzsch, B. - Pavlínková, Gabriela
Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers.
Molecular Neurobiology. Roč. 57, č. 12 (2020), s. 5307-5323. ISSN 0893-7648. E-ISSN 1559-1182
Grant CEP: GA MŠMT(CZ) LM2015062
Institucionální podpora: RVO:86652036
Klíčová slova: bHLH genes * Ear neurosensory development * Neuronal differentiation
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 5.590, rok: 2020
Způsob publikování: Open access
https://link.springer.com/article/10.1007%2Fs12035-020-02092-0

Ear development requires the transcription factors ATOH1 for hair cell differentiation and NEUROD1 for sensory neuron development. In addition, NEUROD1 negatively regulatesAtoh1gene expression. As we previously showed that deletion of theNeurod1gene in the cochlea results in axon guidance defects and excessive peripheral innervation of the sensory epithelium, we hypothesized that some of the innervation defects may be a result of abnormalities in NEUROD1 and ATOH1 interactions. To characterize the interdependency of ATOH1 and NEUROD1 in inner ear development, we generated a newAtoh1/Neurod1double null conditional deletion mutant. Through careful comparison of the effects of singleAtoh1orNeurod1gene deletion with combined doubleAtoh1andNeurod1deletion, we demonstrate that NEUROD1-ATOH1 interactions are not important for theNeurod1null innervation phenotype. We report that neurons lackingNeurod1can innervate the flat epithelium without any sensory hair cells or supporting cells left afterAtoh1deletion, indicating that neurons withNeurod1deletion do not require the presence of hair cells for axon growth. Moreover, transcriptome analysis identified genes encoding axon guidance and neurite growth molecules that are dysregulated in theNeurod1deletion mutant. Taken together, we demonstrate that much of the projections of NEUROD1-deprived inner ear sensory neurons are regulated cell-autonomously.
Trvalý link: http://hdl.handle.net/11104/0318910