Homeodomain transcription factors in vertebrates: working together to make a difference

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How do different anatomical features develop with remarkable precision along the body axis of each animal species? We know that this process is determined by a group of proteins belonging to the Hox family. The Hox proteins read and execute instructions encoded in the genome. Each member of the Hox family appears in a well-defined territory of the developing embryo, and recognises specific instructions (most likely DNA sequences) contained in the genome. A puzzling finding is that the Hox specificity, which is central to developmental programs, is entirely lost in a test tube, where all Hox proteins recognise similar DNA sequences. Thus some other essential unknown biochemical factor must be present in the developing embryo. This project will identify Hox functional targets in the genome, and thus reveal the mechanisms that allow Hox proteins to control anatomical development. We will apply state-of-the-art experimental technologies and develop new computational methods to investigate systems where Hox proteins control development and their malfunctioning causes disease. Collectively, these results will identify the fundamental mechanisms that underlie anatomical development in vertebrates and will cast light on how their malfunctioning can result in diseases.