A putative role for IGF2BP3 in primary cilia formation and function in Xenopus

IGF2BP (VICKZ) proteins are highly conserved oncofetal RNA binding proteins (RBPs) that regulate RNA processing at many levels during development, including stabilization, localization and translation. In mammals, expression of IGF2BP1 and IGF2BP3, the two most highly related paralogs, is dramatically down-regulated after birth but upregulated in many cancers. Previous research has shown that in embryogenesis, IGF2BP3 plays a critical role in neural crest cell migration.

IGF2BP1 has been shown to bind mRNAs involved in cilia formation and function such as Gli1 RNA, a transcription factor that is part of the Hedgehog signaling pathway, active in primary cilia. Primary cilia in the GRP (Gastrocoel roof plate) cells play an essential role in establishing the left-right axis during embryo development. Dysfunction in motile and non-motile cilia affects many human organ systems, and is known to cause developmental disorders. We use Xenopus laevis to ask whether IGF2BP3, the IGF2BP paralog present in frogs, plays an important role in the proper formation and/or function of primary cilia.

Our recent results using immunofluorescent show for the first time that IGF2BP3 protein localizes specifically inside the primary cilia axoneme in the GRP. We are currently extending these results by elucidating the effects of abolishing IGF2BP3 on left/right axis formation and determining how knocking-out zygotic gene expression using CRISPR technology will affect cilia formation and left-right asymmetry.

We hope a better understanding of cilia biology will improve the diagnosis and management of cilia-related diseases.