PgmNr Z6261: Zebrafish fin fold regeneration requires proper control of inflammation via macrophage
.

Authors:
T. Hasegawa 1 ; C. Hall 2 ; P. Crosier 2 ; A. Kudo 1 ; A. Kawakami 1


Institutes
1) Tokyo Institute of Technology, Yokohama, Japan; 2) University of Auckland, Auckland, New Zealand.


Abstract:

Elucidation of tissue regeneration mechanism is necessary for the realization of regenerative medicine. Analysis of its mechanism in regenerative animal models such as zebrafish is one of important approaches.

We have adopted the larval fin fold regeneration model and found that the cloche (clo) mutant, which lacks the hematopoietic and endothelial cells, displays a unique phenotype that apoptosis is induced in the regenerative blastema cells. Our analysis suggested that the blastema cells are normally maintained by a factor from the myeloid cells.

Here, we firstly examined which type of the myeloid cell is crucial for blastema maintenance. Knockdown of macrophage differentiation by the morpholino antisense oligo (MO) against interferon regulatory factor 8 (irf8) showed an increase of apoptosis during regeneration. On the other hand, knockdown of neutrophil differentiation by the colony stimulating factor 3 receptor (gcsfr) MO didn’t effect survival of blastema cells. These results suggested that macrophage may play crucial role in the maintenance of blastema.

Next, we performed a transcriptome analysis and found that interleukin1b (il1b), a molecule that plays a central role in inflammatory response, is highly expressed in the clo for a prolonged time. Furthermore, treatment with dexamethasone, an anti-inflammatory reagent, or the il1b knockdown by MO significantly decreased the apoptosis in the clo mutant, suggesting that an excessive and prolonged inflammation is actually a cause for apoptosis in the clo.

Together, our study suggests a scenario that the tissue inflammation is properly regulated by a factor from the macrophage during regeneration.



ZFIN Genetics Index
1. clo
2. il1b