PUBLICATION

Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae

Authors
Lin, M.J., Lee, S.J.
ID
ZDB-PUB-161108-3
Date
2016
Source
Scientific Reports   6: 36188 (Journal)
Registered Authors
Lee, Shyh-Jye
Keywords
Developmental neurogenesis, Neural progenitors
MeSH Terms
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Cell Differentiation*
  • Stathmin/genetics
  • Stathmin/metabolism*
  • Mesencephalon/cytology
  • Mesencephalon/embryology*
  • Neural Stem Cells/cytology
  • Neural Stem Cells/metabolism*
  • Animals
  • Wnt Signaling Pathway*
(all 13)
PubMed
27819330 Full text @ Sci. Rep.
Abstract
A 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 of stmn4 was mutually exclusive to a pan-neuronal marker, elavl3 that indicates its role in regulating neurogenesis. We showed the knockdown or overexpression of stmn4 resulted in premature neuronal differentiation in dorsal midbrain. We also generated stmn4 maternal-zygotic knockout zebrafish by the CRISPR/Cas9 system. Unexpectedly, only less than 10% of stmn4 mutants showed similar phenotypes observed in that of stmn4 morphants. It might be due to the complementation of the increased stmn1b expression observed in stmn4 mutants. In addition, time-lapse recordings revealed the changes in cellular proliferation and differentiation in stmn4 morphants. Stmn4 morphants displayed a longer G2 phase that could be rescued by Cdc25a. Furthermore, the inhibition of Wnt could reduce stmn4 transcripts. These results suggest that the Wnt-mediated Stmn4 homeostasis is crucial for preventing dorsal midbrain from premature differentiation via the G2 phase control during the neural keel stage.
Genes / Markers
Figures
Figure Gallery (9 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
rw0130aTgTransgenic Insertion
    twu0101
      Small Deletion
      twu0102
        Small Deletion
        w32TgTransgenic Insertion
          1 - 4 of 4
          Show
          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          stmn4CRISPR1-stmn4CRISPR
          stmn4CRISPR2-stmn4CRISPR
          stmn4CRISPR3-stmn4CRISPR
          stmn4MO1-stmn4MRPHLNO
          stmn4MO2-stmn4MRPHLNO
          tp53MO4-tp53MRPHLNO
          1 - 6 of 6
          Show
          Fish
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          GFPEFGGFP
          KaedeEFGKaede
          1 - 2 of 2
          Show
          Mapping
          No data available