Cellular dynamics and molecular mechanisms underlying the 3D organization and connectivity of the statoacoustic ganglion
The statoacoustic ganglion (SAG) is a complex 3D structure composed by neurons in charge of transmitting the information from inner ear hair cells to the CNS. During development, SAG copes with otic tissue demands to maintain functionality. However, SAG development in coordination with otic developm...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/687790 |
| Acceso en línea: | http://hdl.handle.net/10803/687790 |
| Access Level: | acceso abierto |
| Palabra clave: | Statoacoustic ganglion Pioneer cells CRISPR Cell migration Axonogenesis Ganglio estatoacústico Células pioneras Migración celular Axonogénesis 616.8 |
| Sumario: | The statoacoustic ganglion (SAG) is a complex 3D structure composed by neurons in charge of transmitting the information from inner ear hair cells to the CNS. During development, SAG copes with otic tissue demands to maintain functionality. However, SAG development in coordination with otic development has not been addressed in detail. We use high resolution confocal imaging of otic neuroblasts (NB), photoconversion, photoablation, transgenic lines, CRISPR/Cas9 and Cas13 to address SAG development at the molecular and cellular levels. We find a population of pioneer SAG neurons specified outside the otic placode, which play an attracting role over delaminating NB affecting its coalescence. NB from the otic epithelium delaminate in an EMT-like manner, and non-collectively and actively migrate depending on RhoGTPases to establish the anterior SAG lobe. Followingly, NB crawl onto pioneer axons to form the posterior SAG lobe. Lack of both pioneer SAG neurons and pioneer axons alters SAG shape. Finally, we uncover the cell adhesion molecule Cntn2 and the chemokine Cxcl14 as two new molecules required for correct pioneer axon targeting to HC and posterior lobe formation. We confirm that HC and neurotrophin signaling is not required for directed axon targeting but stabilization and neuronal survival. In conclusion, SAG development is a complex process in which several mechanisms interplay, prime and scaffold further SAG developmental steps. |
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