Transcriptional Targets and Effectors of ZFP568, A Krab Zinc Finger Protein Required for Mammalian Convergent Extension

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The acquisition of shape by tissues and organs during embryogenesis requires coordinated cell rearrangements. An elegant example of how the reorganization of cells help to shape the embryo is the process of convergent extension. This process was first described in 1895, when investigators observed that pins sparsely inserted in fish embryos converged towards a central location as the embryo developed, and that these movements correlated with the transformation of the embryo from a rounded ball of cells to an elongated (or extended) structure with anterior-posterior polarity. Since then, more sophisticated techniques have revealed that convergent extension promotes elongation of embryonic structures in a variety of model organisms and developmental contexts. Convergent extension has been widely studied in frogs, fish and flies, but the cellular and molecular mechanisms that control this process in mammals are less well understood. This project focuses on the study of ZFP568, a Krüppel-Associated-Box (KRAB) Zinc finger transcription factor required for convergent extension in mouse. This project uses genetic and molecular approaches to identify the transcriptional targets and effectors of ZFP568. Because KRAB domain proteins are transcriptional regulators exclusively present in the genomes of higher vertebrates, results will shed light on the molecular events that regulate convergent extension specifically in these organisms. Conditions that affect convergent extension cause severe embryonic malformations. Therefore, by increasing our understanding of the mechanisms that control early mammalian morphogenesis, this study will have a broad impact on the developmental biology scientific community. Scientific education and training will be provided to graduate and undergraduate students as an integral part of the project. The PI and lab also participate in educational outreach activities that promote public awareness of Developmental Biology.