Münch, J., González-Rajal, A., and de la Pompa, J.L. (2013) Notch regulates blastema proliferation and prevents differentiation during adult zebrafish fin regeneration. Development (Cambridge, England). 140(7):1402-1411.
Zebrafish have the capacity to regenerate several organs, including the heart and fins. Fin regeneration is epimorphic, involving
the formation at the amputation plane of a mass of undifferentiated, proliferating mesenchymal progenitor-like cells, called
blastema. This tissue provides all the cell types that form the fin, so that after damage or amputation the fin pattern and
structure are fully restored. How blastema cells remain in this progenitor-like state is poorly understood. Here, we show
that the Notch pathway plays an essential role during fin regeneration. Notch signalling is activated during blastema formation
and remains active throughout the regeneration process. Chemical inhibition or morpholino-mediated knockdown of Notch signalling
impairs fin regeneration via decreased proliferation accompanied by reduced expression of Notch target genes in the blastema.
Conversely, overexpression of a constitutively active form of the Notch1 receptor (N1ICD) in the regenerating fin leads to
increased proliferation and to the expansion of the blastema cell markers msxe and msxb, as well as increased expression of the proliferation regulator aldh1a2. This blastema expansion prevents regenerative fin outgrowth, as indicated by the reduction in differentiating osteoblasts
and the inhibition of bone regeneration. We conclude that Notch signalling maintains blastema cells in a plastic, undifferentiated
and proliferative state, an essential requirement for fin regeneration.