Notch signalling in spinal cord patterning: Crosstalk and fate decisions

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dc.contributor.advisorHuang, Peng
dc.contributor.authorJacobs, Craig Timothy
dc.contributor.committeememberHansen, David
dc.contributor.committeememberBrook, William
dc.date2021-11
dc.date.accessioned2021-07-19T22:04:48Z
dc.date.available2021-07-19T22:04:48Z
dc.date.issued2021-07-19
dc.description.abstractThe spinal cord is a highly complex structure. During development, initially equivalent neural progenitors divide and give rise to a specific pattern of differentiated neurons. Understanding how this pattern arises would have far reaching impact, not just in developmental biology but also in the understanding of developmental disorders. Building on the decades of work from other groups, this thesis focuses on the extrinsic cues that guide pattern formation in the zebrafish spinal cord, with particular focus on the highly conserved Notch signalling pathway. The major, and most well studied, role of Notch signalling during neural development is progenitor maintenance. This thesis explores the additional roles of Notch signalling in signalling crosstalk and cell fate decisions. The action of Hedgehog signalling during spinal cord development is well characterised, providing the spatial information to drive the patterning of the ventral neural progenitors. In chapter two, I reveal a novel mechanism by which Notch signalling maintains Hedgehog response in spinal cord progenitors. This occurs at the level of the Gli family of downstream transcription factors, not at the primary cilia as previous reports suggest. This raises the interesting question of whether the Notch mediated control of Hh signalling is providing the instructive cues that guide fate determination in the ventral spinal cord. In chapter three, I analyse this through examining the Notch signalling dynamics of the lateral floor plate domain. This reveals that different cell types in the lateral floor plate display discrete durations of Notch signalling. It is the duration of Notch signalling that instructs cell fate determination, as prolonged exposure is required for the later-born cell fates. How the neighbouring progenitors in the lateral floor plate temporally restrict their Notch response remains an open question, though it is likely mediated through differential ligand-receptor interactions. Collectively, this thesis highlights the pleiotropic nature of Notch signalling during neural development. Alongside the classical involvement in progenitor maintenance, Notch signalling also functions to maintain cellular response to key developmental signals and directly guide cell fate decisions.en_US
dc.identifier.citationJacobs, C. T. (2021). Notch signalling in spinal cord patterning: Crosstalk and fate decisions (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/39026
dc.identifier.urihttp://hdl.handle.net/1880/113652
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectDevelopmental Biologyen_US
dc.subjectCell signallingen_US
dc.subjectSpinal corden_US
dc.subjectZebrafishen_US
dc.subject.classificationBiology--Cellen_US
dc.subject.classificationBiology--Molecularen_US
dc.subject.classificationNeuroscienceen_US
dc.titleNotch signalling in spinal cord patterning: Crosstalk and fate decisionsen_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineMedicine – Biochemistry and Molecular Biologyen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrueen_US
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