Further Development 22.9: Notum Heads Wnt off at the Slice

Regeneration: The Development of Rebuilding

What do anterior cells do to protect themselves from Wnt signaling? In Chapter 4, we discussed one such Wnt inhibitor, called Notum (see Figure 4.25), which in planarians is specifically expressed at the apex of the head in opposition to the posterior Wnt expression. Notum is upregulated in the anterior-facing blastema (see Figure 22.20D, E). Not surprisingly, it was found that notum expression is downregulated in regeneration-deficient species (Lui et al. 2013). Moreover, transcriptome analysis of blastemas in regenerating planarians found that only 1 out of 4,401 genes examined was differentially expressed between anterior- and posterior-facing blastemas! That gene was Notum, expressed only in the anterior blastema (Wurtzel et al. 2015). If Notum expression is knocked down, causing too much Wnt to become functionally active, the anterior-facing blastema will form a tail (Petersen and Reddien 2011). These results strongly suggest that the anterior expression of Notum functions to antagonize the posteriorly produced Wnt, leading to head specification. It has also been proposed that regulation of the balance between Wnt and Notum signals may underlie not only head-tail specification but also regulation of organ size (Hill and Petersen 2015). There also appears to be an anterior-to-posterior gradient of Erk signaling that functions as a positive inducer of head specification. Wnt signaling achieves its repression of head regeneration by inhibiting Erk. Therefore, only in those more anterior regions lacking Wnt (due to Notum’s repression of Wnt) can Erk induce head regeneration (see Figure 22.20F; Umesono et al. 2013).

Literature Cited

Hill, E. M. and C. P. Petersen. 2015. Wnt/Notum spatial feedback inhibition controls neoblast differentiation to regulate reversible growth of the planarian brain. Development 142: 4217–4229.
PubMed Link

Liu, S. Y., C. Selck, B. Friedrich, R. Lutz, M. Vila-Farré, A. Dahl, H. Brandl, N. Lakshmanaperumal, I. Henry and J. C. Rink. 2013. Reactivating head regrowth in a regeneration-deficient planarian species. Nature 500: 81–84.
PubMed Link

Petersen, C. P. and P. W. Reddien. 2011. Polarized notum activation at wounds inhibits Wnt function to promote planarian head regeneration. Science 332: 852–855.
PubMed Link

Umesono, Y., J. Tasaki, Y. Nishimura, M. Hrouda, E. Kawaguchi, S. Yazawa, O. Nishimura, K. Hosoda, T. Inoue and K. Agata. 2013. The molecular logic for planarian regeneration along the anterior-posterior axis. Nature 500: 73–76.
PubMed Link

Wurtzel, O., L. E. Cote, A. Poirier, R. Satija, A. Regev and P. W. Reddien. 2015. A generic and cell-type-specific wound response precedes regeneration in planarians. Dev. Cell 35: 632–645.
PubMed Link

 

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