CaltechTHESIS
  A Caltech Library Service

Interpretation and scaling of positional information during development

Citation

Nahmad Bensusan, Marcos (2011) Interpretation and scaling of positional information during development. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechTHESIS:10212010-000757213

Abstract

Cells in a developing animal require information about their relative position in order to function and differentiate appropriately. In the classical view, cellular positional information is interpreted from the concentration of chemical signals known as morphogens. However, recent studies have questioned the ability of morphogens to establish gene expression patterns in a concentration-dependent manner. Here we combine theoretical tools and experimental work in Drosophila melanogaster to investigate the mechanisms by which positional information is interpreted from a morphogen gradient and the ability of patterns to scale with respect to the size of the system. First, we study how a concentration gradient of the signaling molecule Hedgehog establishes multiple patterns of gene expression along the anterior-posterior axis of the Drosophila wing disc. Using mathematical modeling as a hypotheses-generating tool, we predicted that positional information cannot be explained by different concentration thresholds from a static Hedgehog gradient. Instead, we propose that cells take into account their history of Hedgehog signaling exposure to determine patterns of gene expression. We provide experimental evidence that supports our model and conclude that gradient dynamics, resulting from the gene network architecture of the Hedgehog signaling pathway, determine pattern formation in the wing disc. Second, we introduce a theoretical formalism to study the role of morphogen gradient dynamics in developmental patterning. Given a mathematical model of pattern formation, we define and compute parameter perturbations that leave invariant the steady-state distribution of the relevant morphogen. We propose that this approach can be used as a tool to design genetic experiments that assay the function of morphogen dynamics. Lastly, we use dorsal-ventral patterning of the early Drosophila embryo as a model to study scaling of gene expression patterns with respect to natural variations in axis length, that is, the ability to establish positional information relative to the size of the system. We provide evidence that gene expression patterns that depend on the maternal factor Dorsal, scale along the dorsal-ventral axis. Our data suggest that scaling in this system is a gene-dependent rather than a position-dependent property. We propose that the mechanisms for scaling depend on feedback interactions downstream of Dorsal.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Developmental Patterning, Morphogens, Signaling Dynamics, Scaling, Mathematical Modeling
Degree Grantor:California Institute of Technology
Division:Engineering and Applied Science
Major Option:Control and Dynamical Systems
Minor Option:Biology
Awards:Everhart Lecture Series
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Stathopoulos, Angelike (advisor)
  • Doyle, John Comstock (advisor)
Thesis Committee:
  • Stathopoulos, Angelike (chair)
  • Doyle, John Comstock
  • Murray, Richard M.
  • Rothenberg, Ellen V.
  • Lander, Arthur D.
Defense Date:27 September 2010
Author Email:nahmad (AT) caltech.edu
Funders:
Funding AgencyGrant Number
NIHR01-GM078992
Record Number:CaltechTHESIS:10212010-000757213
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:10212010-000757213
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6150
Collection:CaltechTHESIS
Deposited By: Marcos Nahmad Bensusan
Deposited On:01 Nov 2010 21:11
Last Modified:16 Apr 2013 23:09

Thesis Files

[img]
Preview
PDF (Full Thesis File) - Final Version
See Usage Policy.

17Mb
[img]
Preview
PDF (Cover, Acknowledgments, Abstract, and Contents) - Final Version
See Usage Policy.

107Kb
[img]
Preview
PDF (Chapter 1) - Final Version
See Usage Policy.

236Kb
[img]
Preview
PDF (Chapter 2) - Final Version
See Usage Policy.

5Mb
[img]
Preview
PDF (Chapter 3)
See Usage Policy.

1448Kb
[img]
Preview
PDF (Chapter 4)
See Usage Policy.

4017Kb
[img]
Preview
PDF (Chapter 5) - Final Version
See Usage Policy.

287Kb
[img]
Preview
PDF (Chapter 6) - Final Version
See Usage Policy.

167Kb
[img]
Preview
PDF (Bibliography) - Final Version
See Usage Policy.

206Kb
[img]
Preview
PDF (Appendices) - Supplemental Material
See Usage Policy.

6Mb

Repository Staff Only: item control page