A fundamental challenge in developmental biology is to understand how regulatory networks transform regulatory information into cell fate specification and differentiation. Addressing this challenge requires a comprehensive analysis of the regulatory connections between the transcription factors present in a cell and their regulatory and structural targets through developmental time. The sea urchin aboral ectoderm provides an excellent system to dissect these connections due to its accessibility to quantitative expression studies and the multiple developmental programs executed in this territory. One of these programs drives the differentiation of the entire aboral ectoderm into squamous epithelium and represses neural fate, while other programs define regulatory sub-domains within the aboral ectoderm important to normal morphogenesis of other embryonic territories. These programs depend strongly on the BMP pathway, a highly conserved regulator of ecotdermal patterning. Here we propose to identify the downstream targets of the aboral ectoderm regulatory network and to construct a mechanistic model of the aboral ectoderm specification and differentiation. We will conduct a genome-wide identification of (1) cis-regulatory elements that the aboral ectoderm transcription factors bind to (2) genes that respond to perturbation of the aboral ectoderm transcription factors. The function of identified cis-regulatory elements will be tested using a new high-throughput technology. The expression of key target genes will be perturbed and their effect on the aboral ectoderm morphology and embryogenesis will be studied. Based on this analysis we will construct a mathematical model that simulates the dynamic function of the aboral ectoderm regulatory network. Thus, this project will provide unprecedented understanding of the dynamic regulation of an entire developmental process, from regulatory state establishment to the acquisition of cellular and morphological properties.
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