| dc.contributor.advisor | Marquardt, Till Prof. Dr. | de |
| dc.contributor.author | Poh, Chor Hoon | de |
| dc.date.accessioned | 2013-06-19T08:53:47Z | de |
| dc.date.available | 2013-06-19T08:53:47Z | de |
| dc.date.issued | 2013-06-19 | de |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-001F-E835-6 | de |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-3893 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | The role of innervation during mouse embryonic myogenesis: what molecular genetics tells | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Nave, Klaus-armin Prof. Dr. | de |
| dc.date.examination | 2013-03-08 | de |
| dc.description.abstracteng | The interdependency of motor neurons and the skeletal muscle is a classical example for instructive and trophic tissue interactions during development and adult life. It is well established that skeletal muscles undergo atrophy in the absence of motor neuron innervation. In the adult, molecular pathways underlying the dependency of muscle fibers on innervation have begun to emerge. However, it is much less clear how and to what extent motor neuronal input contributes to myogenesis during embryonic development. Previous studies using manual dissection and systemic application of pharmacological paralyzing agents have led to two main yet divergent conclusions on the myogenic requirements from the nerve as well as the myogenic response to denervation.
The aim of my thesis project was to resolve these issues through selective gene manipulation in the mouse. Targeted genetic suppression of motor neuron generation, leaving skeletal muscle from the outset devoid of motor innervation, did not affect the formation of primary or secondary myotubes. At the same time, however, the absence of motor innervation completely prevented terminal differentiation of myotubes into functionally contractile fibers and resulted in their progressive apoptotic elimination. This in turn led to a compensatory proliferation of satellite cells to make up for muscle fiber loss. The impacts caused by wholesale removal of motor innervation were faithfully phenocopied in the absence of cholinergic neuromuscular transmission. On the other hand, milder skeletal muscle hypoplasia was observed after selective genetic suppression of evoked, but not spontaneous neuromuscular transmission. Transcriptome profiling revealed a unique immediate early response of myotubes lacking motor innervation that differed from the pathways operating during adult denervation. Herein, embryonic innervation appears to operate through a dedicated set of myogenic transcription factors previously implicated in muscle fiber terminal differentiation. Taken together, my studies provide conclusive evidence that motor innervation is dispensable for the principal formation of both primary and secondary myotubes, but is absolutely required for their terminal differentiation into contractile fibers and subsequent survival, thus resolving a long-standing controversy surrounding the role of innervation in skeletal myogenesis. I further found that developmental and adult innervation operate through distinct molecular pathways to promote muscle fiber differentiation and survival, and identified a candidate myogenic program which may underlie innervation-dependent embryonic myogenesis. | de |
| dc.contributor.coReferee | Pieler, Tomas Prof. Dr. | de |
| dc.subject.eng | innervation | de |
| dc.subject.eng | myogenesis | de |
| dc.subject.eng | mouse | de |
| dc.subject.eng | molecular genetics | de |
| dc.subject.eng | muscle | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-001F-E835-6-8 | de |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 749814365 | de |