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

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
anos1a	anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+	standard conditions	Prim-15	Not Detected	posterior lateral line primordium	ISH	Fig. S3
anos1a	WT	standard conditions	Prim-5		posterior lateral line primordium	ISH	Fig. S3
anos1a	WT	standard conditions	Prim-15		posterior lateral line primordium	ISH	Fig. S3
anos1a	WT	standard conditions	20-25 somites		posterior lateral line primordium	ISH	Fig. S3
anos1a	zf106Tg	standard conditions	Prim-15		posterior lateral line primordium	ISH	Fig. 3
anos1b	anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+	standard conditions	Prim-15	Not Detected	posterior lateral line primordium	ISH	Fig. S3
anos1b	WT	standard conditions	Prim-5		posterior lateral line primordium	ISH	Fig. S3
anos1b	WT	standard conditions	Prim-15		posterior lateral line primordium	ISH	Fig. S3
anos1b	zf106Tg	standard conditions	Prim-15		posterior lateral line primordium	ISH	Fig. 3
EGFP	anos1a^sk50/sk50; zf106Tg	standard conditions	Long-pec		posterior lateral line neuromast	IFL	Fig. S3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO4-atoh1a	standard conditions	Long-pec	posterior lateral line neuromast decreased amount, abnormal	Fig. 1
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+	standard conditions	Prim-15	neuromast decreased size, abnormal	Fig. 3
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+	standard conditions	Prim-15	posterior lateral line primordium anos1a expression absent, abnormal	Fig. S3
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+	standard conditions	Prim-15	posterior lateral line primordium anos1b expression absent, abnormal	Fig. S3
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+	standard conditions	High-pec	posterior lateral line neuromast decreased amount, abnormal	Fig. 3
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+	standard conditions	Long-pec	posterior lateral line neuromast decreased amount, abnormal	Fig. 1
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+ + MO4-atoh1a	standard conditions	Long-pec	posterior lateral line neuromast decreased amount, abnormal	Fig. 1
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+ + MO4-atoh1a	standard conditions	Long-pec	posterior lateral line neuromast decreased amount, exacerbated	Fig. 1
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+; kyu2Tg; sk85Tg	standard conditions	Prim-25	posterior lateral line primordium GFP expression increased distribution, abnormal	Fig. 3
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+; sk85Tg; sk89Tg + MO4-atoh1a	standard conditions	Prim-15	posterior lateral line primordium EGFP expression decreased amount, abnormal	Fig. 4

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
kyu2Tg	Tg(OTM:d2EGFP)	Transgenic Insertion
pd1Tg	Tg(hsp70l:dnfgfr1a-EGFP)	Transgenic Insertion
pt6Tg	Tg(dusp6:d2EGFP)	Transgenic Insertion
sk50		Small Deletion	anos1a
sk51		Small Deletion	anos1a
sk52		Small Deletion	anos1b
sk53		Small Deletion	anos1b
sk79Tg	TgBAC(cxcr4b:cxcr4b-mKate2-IRES-EGFP-CAAX,cryaa:DsRed)	Transgenic Insertion
sk85Tg	Tg(-7.2sox10:LY-mCherry)	Transgenic Insertion
sk86Tg	Tg(hsp70l:anos1b)	Transgenic Insertion

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
anos1a	TALEN1-anos1a	TALEN
anos1b	TALEN1-anos1b	TALEN
atoh1a	MO4-atoh1a	MRPHLNO

Fish

Fish
anos1a^sk50/sk50; zf106Tg
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+; kyu2Tg; sk85Tg
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+ + MO4-atoh1a
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+; pt6Tg; sk85Tg
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+; sk79Tg
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+; sk85Tg; sk89Tg
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+; sk85Tg; sk89Tg + MO4-atoh1a
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+; sk89Tg
anos1a^sk50/+; anos1a^sk51/+; anos1b^sk52/+; anos1b^sk53/+; sk89Tg; zf106Tg

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
d2EGFP	EFG	d2EGFP
DsRed	EFG	DsRed
ECFP	EFG	ECFP
EGFP	EFG	EGFP
GFP	EFG	GFP
mCherry	EFG	mCherry
mKate2	EFG	mKate2
TagRFP	EFG	TagRFP

Mapping

Wang et al., 2018 ZDB-PUB-180821-3 PMID:30122631

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

Wang et al., 2018

ZDB-PUB-180821-3
PMID:30122631