IP6 in Left-Right Asymmetry

Science's STKE  12 Jul 2005:
Vol. 2005, Issue 292, pp. tw252
DOI: 10.1126/stke.2922005tw252

All embryos start out bilaterally symmetrical, and in response to a directed flow of extracellular fluid (nodal flow), this symmetry is broken. Sarmah et al. show that in zebrafish embryos, embryo asymmetry is dependent on inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IPK1, encoded by ipk1), which catalyzes the formation of inositol 1,2,3,4,5,6-phosphate (IP6). Knockdown of ipk1 using three different methods resulted in accumulation of IP4 and IP5 (an indication of loss of IPK1 activity) and randomization of heart placement and positioning of visceral organs (based on expression of various genes normally expressed at higher levels on one side). Furthermore, brain asymmetry was also disrupted in the absence of IPK1. Loss of IPK1 did not disrupt formation of the ciliated cells of the Kupffer's vesicle (KV), which is believed to be the source of the nodal flow in zebrafish embryos, and this suggests that IP6 may be important for downstream signaling in response to the nodal flow as opposed to generation of nodal flow. Knockdown of ipk1 resulted in loss of calcium signaling in the KV region. Thus, IPK1 activity, presumably leading to the production of IP6, appears to be required for calcium signaling in response to nodal flow.

B. Sarmah, A. J. Latimer, B. Appel, S. R. Wente, Inositol polyphosphates regulate zebrafish left-right asymmetry. Dev. Cell 9, 133-145 (2005). [PubMed]