Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae
Journal
Scientific Reports
Journal Volume
6
Date Issued
2016
Author(s)
Abstract
AbstractA delicate balance between proliferating and differentiating signals is necessary to ensure proper growth and neuronal specification. By studying the developing zebrafish brain, we observed a specific and dynamic expression of a microtubule destabilizer gene,stathmin-like 4(stmn4), in the dorsal midbrain region. The expression ofstmn4was mutually exclusive to a pan-neuronal marker,elavl3that indicates its role in regulating neurogenesis. We showed the knockdown or overexpression ofstmn4resulted in premature neuronal differentiation in dorsal midbrain. We also generatedstmn4maternal-zygotic knockout zebrafish by the CRISPR/Cas9 system. Unexpectedly, only less than 10% ofstmn4mutants showed similar phenotypes observed in that ofstmn4morphants. It might be due to the complementation of the increasedstmn1bexpression observed instmn4mutants. In addition, time-lapse recordings revealed the changes in cellular proliferation and differentiation instmn4morphants.Stmn4morphants displayed a longer G2phase that could be rescued by Cdc25a. Furthermore, the inhibition of Wnt could reduce stmn4transcripts. These results suggest that the Wnt-mediated Stmn4 homeostasis is crucial for preventing dorsal midbrain from premature differentiation via the G2phase control during the neural keel stage.
Type
journal article