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Genome Activation and Regulation of Signaling in the Rapidly Dividing Drosophila Embryo

Citation

Sandler, Jeremy Edward (2017) Genome Activation and Regulation of Signaling in the Rapidly Dividing Drosophila Embryo. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9K935KD. http://resolver.caltech.edu/CaltechTHESIS:05112017-102839369

Abstract

Embryonic development of the fruit fly Drosophila melanogaster is unique among model organisms and animals in general, as rapid and syncytial nuclear divisions characterize the early stages before cell membranes form. These nuclear divisions occur every eight to fifteen minutes, culminating with a 45-minute cell cycle where cell membranes form and the 6000 nuclei become 6000 cells before the embryo undergoes gastrulation. At the beginning of development, maternally deposited transcripts define the major axes of the embryo and control all processes that occur. As the syncytial nuclear cycles slow and nuclei migrate to the periphery of the embryo, maternal transcripts are degraded and the zygotic genome is first activated. The rapid pace of nuclear divisions concurrent with the activation of the zygotic genome presents unique challenges to the developing embryo, as the constraints imposed by mitosis limit the ability to transcribe new genes. This switch of control, the Maternal to Zygotic Transition, has been the subject of studies at the molecular and genetic level for almost 30 years. Here, we use new tools and approaches to study the developing embryo at a time scale not previously achieved. We show how the gene regulatory network along the dorsal-ventral axis, including entire signaling pathways, is activated using time point intervals of 10 minutes. Using mutants, we show the contribution of individual genes in the process of development and the resulting changes in expression levels for the entire network. Finally, we examine the transcription of long genes during the rapid syncytial nuclear cycles, when time constraints limit the ability to transcribe the entire gene. We show how an RNA binding protein regulates the truncation of the transcripts into short isoforms with novel coding sequences, and how these short gene products code for functional proteins that regulate the spatiotemporal activation of key signaling pathways in the embryo.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Drosophila, development, embryogenesis, cell signaling, transcription, genetics
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Biology
Awards:Lawrence L. and Audrey W. Ferguson Prize, 2017.
Thesis Availability:Withheld
Research Advisor(s):
  • Stathopoulos, Angelike
Thesis Committee:
  • Sternberg, Paul W. (chair)
  • Bronner, Marianne E.
  • Rothenberg, Ellen V.
  • Stathopoulos, Angelike
  • Davidson, Eric H.
Defense Date:24 May 2017
Funders:
Funding AgencyGrant Number
National Institutes of HealthR01GM077668
National Institutes of HealthR35GM118146
NIH NRSA5T32GM07616
Record Number:CaltechTHESIS:05112017-102839369
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:05112017-102839369
DOI:10.7907/Z9K935KD
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.tig.2016.04.004DOIArticle adapted for Chapter 1.
http://dx.doi.org/10.1534/genetics.116.186783DOIArticle adapted for Chapter 2.
ORCID:
AuthorORCID
Sandler, Jeremy Edward0000-0001-8340-7583
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10162
Collection:CaltechTHESIS
Deposited By: Jeremy Sandler
Deposited On:06 Jun 2017 23:47
Last Modified:24 Apr 2018 22:19

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