Grant: $236,455 - National Institutes of Health - Jul. 16, 2009
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Award Description: Deciphering how signals between cells coordinate heart development is essential for the diagnosis and treatment of congenital heart disorders. Our long-term goal is to gain a comprehensive understanding of how one of these signals, fibroblast growth factor (FGF) impacts early heart formation. To achieve this we proposed a series of experiments designed to exploit the cellular and genetic simplicity of Ciona intestinalis, a close evolutionary relative of the vertebrates. Our specific hypothesis is that a broad FGF signal is refined by limiting downstream activation of the Ets transcription factor. This hypothesis is based on three observations: 1) Heart specification in Ciona requires post-transciptional activation of Ets downstream of FGF signaling. 2) Ets expression is limited to four founder cells. 3) FGF drives asymmetric division/specification within the Ets expressing founder cell lineage. We proposed to study both transcriptional and post-transcriptional mechanisms involved in limiting Ets mediated heart specification. The first aim focused on determing how Ets transcription is restricted to a small group of heart 'founder cells.' The second and third aims focused on two potential mechanisms that may restrict post-transcriptional activation of Ets within heart founder cell progeny; A) exposure to different levels of FGF (the gradient model) or; B) differences in the ability of founder cell progeny to respond to FGF (the competence model). This supplemental grant entails a new set of studies encompassed by Aim 3 of the parent grant. Proposed supplemental studies will test a newly developed model for differential competence. According to the new model, polarized CDC42 activity determines whether founder lineage cells respond to FGF signaling.
Project Description: As defined in the Award Description field.
Jobs Summary: Prime Recipient Retained: Research Associate (Total jobs reported: 1)
Project Status: Less Than 50% Completed
This award's data was last updated on Jul. 16, 2009. Help expand these official descriptions using the wiki below.