Materna, Stefan Christian (2012) The regulatory origin of oral and aboral mesoderm in sea urchin embryos. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechTHESIS:05122012-162210497
Gene regulatory networks (GRN) underlie the control processes that are executed during embryonic development. Their constituents are transcription factors that regulate downstream targets, including other transcription factors. The regulatory architecture of a GRN reveals how discrete developmental tasks, such as cell specification, are implemented.
We here expand the GRN underlying development of sea urchin non-skeletogenic mesoderm (NSM). NSM cells are the offspring of the inner ring of the veg2 cells that lie adjacent to the skeletogenic mesoderm (SM) and receive the Delta signal presented by these cells. Perturbation of Delta reveals that all NSM-specific genes are activated by Delta, but also indicate that Delta has few direct targets. A large number of genes are activated only after delta expression in the SM disappears, thus indicating that these genes are indirect targets and downstream of early NSM transcription factors. We show that the second phase of delta expresion (in the NSM) activates the foxY gene; loss of NSM Delta does not interfere with early NSM specification but instead abolishes development of late mesoderm derivates.
NSM is partitioned into an oral and an aboral segment as a consequence of Nodal signaling. However, Nodal activates the homeobox gene not, which represses early NSM genes on the oral side, causing them to become restricted to the aboral side. This allows oral NSM genes to be activated. Oral NSM genes can be expressed throughout the entire NSM if aboral NSM specification is perturbed. This shows that the driver of NSM genes is present throughout the NSM, making SM Delta a likely candidate. We examine the regulatory state of oral and aboral NSM segments and show that a GRN subcircuit on the aboral side locks down its expression. The sets of regulatory genes on both sides of the NSM are entirely distinct and mutually exclusive.
|Item Type:||Thesis (Dissertation (Ph.D.))|
|Subject Keywords:||sea urchin; gene regulatory network; development; mesoderm; specification; Delta/Notch, Nodal, transcription factor|
|Degree Grantor:||California Institute of Technology|
|Major Option:||Biochemistry and Molecular Biophysics|
|Thesis Availability:||Public (worldwide access)|
|Defense Date:||20 September 2011|
|Non-Caltech Author Email:||stefanmaterna (AT) gmail.com|
|Default Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Stefan Materna|
|Deposited On:||15 May 2012 23:02|
|Last Modified:||26 Dec 2012 04:42|
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