Signal-dependent regulation of chordate heart gene networks

Project: Research

Investigators

  • Bradley J Davidson (PI)

Description

Signaling between cells plays a key role in heart development. However, the mechanisms that mediate precise transcriptional changes downstream of these cardiogenic signals remain poorly characterized. Deciphering how cardiogenic signaling coordinates heart gene expression is essential for the diagnosis and treatment of congenital heart disorders. Our long-term goal is to gain a comprehensive understanding of cardiogenic signaling and how it impacts chordate heart gene networks. The complexity of this process in vertebrate embryos has hindered progress. We have begun to exploit the simplicity of Ciona robusta, a close evolutionary relative of the vertebrates, to investigate a conserved role for the signal dependent transcription factor, Ets, in early heart development. Our hypothesis is that Ets works in tandem with a lineage-specific co-factor to establish heart progenitor identity. This hypothesis is based on three sets of observations. 1. Ets activity is both necessary and sufficient for heart progenitor gene expression. 2. Paired binding motifs for Ets and a presumptive homeodomain co-factor are required for heart progenitor gene regulation. 3. A bio-informatic search focused on paired Ets+co-factor binding motifs was successfully used for de-novo identification of heart progenitor regulatory elements. The proposed specific aims focus on determining the precise transcriptional role of Ets in the heart progenitor gene network. Our efforts will initially focus on identification of the presumptive Ets co-factor. We will then begin to elucidate how Ets and this co-factor directly regulate a defined set of primary heart genes. If time permits, we will also determine how silencer elements ensure precise, signal-dependent expression of Ets target genes. These efforts will be tailored to promote intensive training of undergraduate researchers in the formulation and execution of independent research projects.
Award amount$154,000.00
Award date01/01/2020
Program typeAHA Institutional Research Enhancement Award (AIRE
Award ID20AIREA35080013
Effective start/end date01/01/202012/31/2021
StatusActive