PUBLICATION

miR-34b regulates multiciliogenesis during organ formation in zebrafish

Authors
Wang, L., Fu, C., Fan, H., Du, T., Dong, M., Chen, Y., Jin, Y., Zhou, Y., Deng, M., Gu, A., Jing, Q., Liu, T., and Zhou, Y.
ID
ZDB-PUB-130703-10
Date
2013
Source
Development (Cambridge, England)   140(13): 2755-2764 (Journal)
Registered Authors
Chen, Yi, Deng, Min, Dong, Mei, Jin, Yi, Zhou, Yi, Zhou, Yong
Keywords
cell migration, kidney, microRNA, multicilliogenesis, olfactory placode, mir34b
Datasets
GEO:GSE46844
MeSH Terms
  • Animals
  • Cell Movement/genetics
  • Cell Movement/physiology
  • Kidney/embryology
  • Kidney/metabolism
  • MicroRNAs/genetics
  • MicroRNAs/physiology*
  • Polymerase Chain Reaction
  • Signal Transduction/genetics
  • Signal Transduction/physiology
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
(all 13)
PubMed
23698347 Full text @ Development
Abstract

Multiciliated cells (MCCs) possess multiple motile cilia and are distributed throughout the vertebrate body, performing important physiological functions by regulating fluid movement in the intercellular space. Neither their function during organ development nor the molecular mechanisms underlying multiciliogenesis are well understood. Although dysregulation of members of the miR-34 family plays a key role in the progression of various cancers, the physiological function of miR-34b, especially in regulating organ formation, is largely unknown. Here, we demonstrate that miR-34b expression is enriched in kidney MCCs and the olfactory placode in zebrafish. Inhibiting miR-34b function using morpholino antisense oligonucleotides disrupted kidney proximal tubule convolution and the proper distribution of distal transporting cells and MCCs. Microarray analysis of gene expression, cilia immunostaining and a fluid flow assay revealed that miR-34b is functionally required for the multiciliogenesis of MCCs in the kidney and olfactory placode. We hypothesize that miR-34b regulates kidney morphogenesis by controlling the movement and distribution of kidney MCCs and fluid flow. We found that cmyb was genetically downstream of miR-34b and acted as a key regulator of multiciliogenesis. Elevated expression of cmyb blocked membrane docking of centrioles, whereas loss of cmyb impaired centriole multiplication, both of which resulted in defects in the formation of ciliary bundles. Thus, miR-34b serves as a guardian to maintain the proper level of cmyb expression. In summary, our studies have uncovered an essential role for miR-34b-Cmyb signaling during multiciliogenesis and kidney morphogenesis.

Genes / Markers
Marker Marker Type Name
bbs2GENEBardet-Biedl syndrome 2
cdk6GENEcyclin dependent kinase 6
creb1aGENEcAMP responsive element binding protein 1a
dnaaf1GENEdynein axonemal assembly factor 1
fam49aGENEfamily with sequence similarity 49 member A
foxj1aGENEforkhead box J1a
foxj1bGENEforkhead box J1b
gab1GENEGRB2-associated binding protein 1
gadd45baGENEgrowth arrest and DNA-damage-inducible, beta a
gata1aGENEGATA binding protein 1a
1 - 10 of 41
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Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hkz3
    Point Mutation
    hkz03tTgTransgenic Insertion
      zf169TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        hoxb8aMO1-hoxb8aMRPHLNO
        mir34bMO1-mir34bMRPHLNO
        mir34bMO2-mir34bMRPHLNO
        mybMO2-mybMRPHLNO
        rfx2MO1-rfx2MRPHLNO
        1 - 5 of 5
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        Fish
        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
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        Mapping
        No data available