PUBLICATION

Anosmin1 Shuttles Fgf to Facilitate Its Diffusion, Increase Its Local Concentration, and Induce Sensory Organs

Authors
Wang, J., Yin, Y., Lau, S., Sankaran, J., Rothenberg, E., Wohland, T., Meier-Schellersheim, M., Knaut, H.
ID
ZDB-PUB-180821-3
Date
2018
Source
Developmental Cell   46(6): 751-766.e12 (Journal)
Registered Authors
Knaut, Holger, Wang, John
Keywords
FGF signaling, Kal1/Anosmin1, Kallmann Syndrome, growth factor diffusion, sensory organ differentiation
MeSH Terms
  • Cell Differentiation
  • Signal Transduction
  • Fibroblast Growth Factor 10/genetics
  • Fibroblast Growth Factor 10/metabolism*
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Animals
  • Zebrafish/growth & development*
  • Zebrafish/physiology
  • Gene Expression Regulation, Developmental*
  • Sense Organs/cytology*
  • Sense Organs/metabolism
  • Morphogenesis*
(all 15)
PubMed
30122631 Full text @ Dev. Cell
Abstract
Growth factors induce and pattern sensory organs, but how their distribution is regulated by the extracellular matrix (ECM) is largely unclear. To address this question, we analyzed the diffusion behavior of Fgf10 molecules during sensory organ formation in the zebrafish posterior lateral line primordium. In this tissue, secreted Fgf10 induces organ formation at a distance from its source. We find that most Fgf10 molecules are highly diffusive and move rapidly through the ECM. We identify Anosmin1, which when mutated in humans causes Kallmann Syndrome, as an ECM protein that binds to Fgf10 and facilitates its diffusivity by increasing the pool of fast-moving Fgf10 molecules. In the absence of Anosmin1, Fgf10 levels are reduced and organ formation is impaired. Global overexpression of Anosmin1 slows the fast-moving Fgf10 molecules and results in Fgf10 dispersal. These results suggest that Anosmin1 liberates ECM-bound Fgf10 and shuttles it to increase its signaling range.
Genes / Markers
Figures
Figure Gallery (10 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO4-atoh1astandard conditionsLong-pec
anos1ask50/+; anos1ask51/+; anos1bsk52/+; anos1bsk53/+standard conditionsPrim-15
anos1ask50/+; anos1ask51/+; anos1bsk52/+; anos1bsk53/+standard conditionsPrim-15
anos1ask50/+; anos1ask51/+; anos1bsk52/+; anos1bsk53/+standard conditionsPrim-15
anos1ask50/+; anos1ask51/+; anos1bsk52/+; anos1bsk53/+standard conditionsHigh-pec
anos1ask50/+; anos1ask51/+; anos1bsk52/+; anos1bsk53/+standard conditionsLong-pec
anos1ask50/+; anos1ask51/+; anos1bsk52/+; anos1bsk53/+ + MO4-atoh1astandard conditionsLong-pec
anos1ask50/+; anos1ask51/+; anos1bsk52/+; anos1bsk53/+ + MO4-atoh1astandard conditionsLong-pec
anos1ask50/+; anos1ask51/+; anos1bsk52/+; anos1bsk53/+; kyu2Tg; sk85Tgstandard conditionsPrim-25
anos1ask50/+; anos1ask51/+; anos1bsk52/+; anos1bsk53/+; sk85Tg; sk89Tg + MO4-atoh1astandard conditionsPrim-15
1 - 10 of 36
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
kyu2TgTransgenic Insertion
    pd1TgTransgenic Insertion
      pt6TgTransgenic Insertion
        sk50
          Small Deletion
          sk51
            Small Deletion
            sk52
              Small Deletion
              sk53
                Small Deletion
                sk79TgTransgenic Insertion
                  sk85TgTransgenic Insertion
                    sk86TgTransgenic Insertion
                      1 - 10 of 21
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      anos1aTALEN1-anos1aTALEN
                      anos1bTALEN1-anos1bTALEN
                      atoh1aMO4-atoh1aMRPHLNO
                      1 - 3 of 3
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                      Fish
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      d2EGFPEFGd2EGFP
                      DsRedEFGDsRed
                      ECFPEFGECFP
                      EGFPEFGEGFP
                      GFPEFGGFP
                      mCherryEFGmCherry
                      mKate2EFGmKate2
                      TagRFPEFGTagRFP
                      1 - 8 of 8
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                      Mapping
                      No data available