Background: Macrophages and neutrophils are key phagocytes in regeneration. Results: Neutrophils are the primary phagocytes in the inflammatory stage and are dispensable for zebrafish fin regeneration, whereas macrophages mainly function in the resolution stage and are required for fin regeneration. Conclusion: Macrophages and neutrophils behave differently during zebrafish fin injury and regeneration. Significance: Our study documents that macrophages and neutrophils play distinct functions in tissue regeneration.
foxD5 is expressed in the nascent neural ectoderm concomitant with several other neural-fate specifying transcription factors. We used loss-of-function and gain-of-function approaches to analyze the functional position of foxD5 amongst these other factors. Loss of FoxD5 reduces the expression of sox2, sox11, soxD, zic1, zic3 and Xiro1-3 at the onset of gastrulation, and of geminin, sox3 and zic2, which are maternally expressed, by late gastrulation. At neural plate stages most of these genes remain reduced, but the domains of zic1 and zic3 are expanded. Increased FoxD5 induces geminin and zic2, weakly represses sox11 at early gastrula but later (st12) induces it; weakly represses sox2 and sox3 transiently and strongly represses soxD, zic1, zic3 and Xiro1-3. The foxD5 effects on zic1, zic3 and Xiro1-3 involve transcriptional repression, whereas those on geminin and zic2 involve transcriptional activation. foxD5’s effects on geminin, sox11 and zic2 occur at the onset of gastrulation, whereas the other genes require earlier foxD5 activity. geminin, sox11 and zic2, each of which is up-regulated directly by foxD5, are all required to account for foxD5 phenotypes, indicating that this triad constitutes a transcriptional network rather than linear path that coordinately up-regulates genes that promote an immature neural fate and inhibits genes that promote the onset of neural differentiation. We also show that foxD5 promotes an ectopic neural fate in the epidermis by reducing BMP signaling. Several of the genes that are repressed by foxD5 in turn reduce foxD5 expression, contributing to the medial-lateral patterning of the neural plate.
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