Ubiquitin conjugation system for body axes specification in vertebrates

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Abstract
The early vertebrate embryonic development is initiated through the crosstalk and collaboration of Wnt, TGF-β (transforming growth factor), and FGF (fibroblast growth factor) signal transductions. The combined action of the signaling pathways regulates expression of several genes which defines dorso–ventral body axis followed by antero–posterior axis and left–right body asymmetry. Thus, dissection of molecular mechanisms, not only at the level of transcriptional control but also post-translational control of signaling outputs, is important for understanding how the body axes are sequentially specified by fine tuning the signaling pathways. Accumulating lines of evidences strongly suggest that the signaling molecules having pivotal roles in carving body plan along with developmental processes must be subjected to regulated protein destruction or nondegradable but ubiquitin-dependent post-translational modification. Protein ubiquitylation exploits a consecutive enzymatic reaction of E1, E2, and E3 proteins to induce 26 proteasome- or lysosome-dependent protein destruction, or cellular signaling, protein trafficking, endocytosis, and others. Since all the signaling pathways involved in early body patterning are also important in the post-embryonic pathogenesis, in-depth functional analysis of the signaling components and their regulatory mechanisms in embryogenesis is required to identify therapeutic targets of diseases. In this review, we will describe how ubiquitin conjugation mechanisms modulate Wnt, TGF-β, and FGF stimuli, thereby establishing the embryonic body plan.
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  • Chungnam National University

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