Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.790549
Title: Nutritional regulation of neural progenitors in Drosophila
Author: Fons, C.
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Abstract:
Suboptimal nutrition during development can alter body proportions and have long- term consequences upon adult health and disease. In developing organisms, growing organs are differentially sensitive to low levels of dietary nutrients. In mammals, a key survival strategy for coping with nutrient deprivation in utero involves sparing the growth of the developing brain at the expense of other organs. Although brain sparing is an important survival response that appears to be highly conserved during evolution, its underlying mechanisms are still unclear. It has been previously shown that CNS sparing is present in Drosophila and the first underlying molecular mechanism for this was identified. Neural stem cell like precursors called neuroblasts deploy Anaplastic lymphoma kinase (Alk) to functionally replace the Insulin receptor and therefore to activate the Pi3K pathway in a constitutive manner even during severe nutrient restriction (NR). In this thesis, I investigate the timing mechanisms that regulate neuroblast proliferation and the onset of CNS sparing during larval development. Surprisingly, I find that the onset of NR-resistant neuroblast proliferation/growth and thus CNS sparing is not temporally coupled with exit from quiescence. Instead, it appears to be activated in a gradual manner during the third larval instar. I find that ecdysone receptor (EcR) signalling in glia regulates neuroblast proliferation specifically during NR. However, in the neuroblast lineage itself, EcR is required for neuroblast growth/proliferation during both NR and fed conditions. I demonstrate that the temporal transcription factors Castor and Seven-Up both regulate the acceleration in neuroblast proliferation that occurs during larval development. Both factors are also required for neuroblast growth and proliferation during NR and so are relevant for neural sparing. These findings support a model where neuroblasts regulate their nutrient sensitivity and proliferation in response to both systemic and cell-autonomous timing cues.
Supervisor: Gould, A. P. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.790549  DOI: Not available
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