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FGFR-related gene nou-darake restricts brain tissues to the head region of planarians

Abstract

The study of planarian regeneration may help us to understand how we can rebuild organs and tissues after injury, disease or ageing1. The robust regenerative abilities of planarians are based upon a population of totipotent stem cells (neoblasts)2,3,4, and among the organs regenerated by these animals is a well-organized central nervous system5,6. In recent years, methodologies such as whole-mount in situ hybridizations and double-stranded RNA have been extended to planarians with the aim of unravelling the molecular basis of their regenerative capacities7,8,9,10,11. Here we report the identification and characterization of nou-darake (ndk), a gene encoding a fibroblast growth factor receptor (FGFR)-like molecule specifically expressed in the head region of the planarian Dugesia japonica. Loss of function of ndk by RNA interference results in the induction of ectopic brain tissues throughout the body. This ectopic brain formation was suppressed by inhibition of two planarian FGFR homologues (FGFR1 and FGFR2). Additionally, ndk inhibits FGF signalling in Xenopus embryos. The data suggest that ndk may modulate FGF signalling in stem cells to restrict brain tissues to the head region of planarians.

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Figure 1: Expression pattern of ndk and predicted structure.
Figure 2: Sequence comparison between the extracellular domains of NDK and the proteins encoded by human FGFRL1 and FGFR3 genes.
Figure 3: Effects of ndk-dsRNA injections during regeneration.
Figure 4: Brain expansion in intact animals.
Figure 5: Effects of ndk- and FGFR-dsRNA injections on regenerating head (a, c, e, g) and trunk (b, d, f, h) fragments.
Figure 6: Effects of ndk mRNA injections into Xenopus embryos.

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Acknowledgements

We thank S. Kuratani for comments on the manuscript, J. Brockes and T. Miyata for promoting collaboration, and D. Turner for pCS2 + and pCS2 + nβ-gal. This work was supported by Special Coordination Funds for Promoting Science and Technology (K.A.), a Grant-in-Aid for Creative Basic Research (K.A. and T.G.), a Grant-in-Aid for Scientific Research on Priority Areas (K.A. and M.T.) and the National Institutes of Health National Institute of General Medical Sciences (A.S.A.).

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Correspondence to Kiyokazu Agata.

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Cebrià, F., Kobayashi, C., Umesono, Y. et al. FGFR-related gene nou-darake restricts brain tissues to the head region of planarians. Nature 419, 620–624 (2002). https://doi.org/10.1038/nature01042

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