PUBLICATION

An Attractive Reelin Gradient Establishes Synaptic Lamination in the Vertebrate Visual System

Authors

Di Donato, V., De Santis, F., Albadri, S., Auer, T.O., Duroure, K., Charpentier, M., Concordet, J.P., Gebhardt, C., Del Bene, F.

ID

ZDB-PUB-180214-4

Date

2018

Source

Neuron 97(5): 1049-1062.e6 (Journal)

Registered Authors

Albadri, Shahad, Auer, Thomas, Del Bene, Filippo, De Santis, Flavia, Di-Donato, Vincenzo, Duroure, Karine, Gebhardt, Christoph

Keywords

Reelin, axon guidance, concentration gradient, optic tectum, synaptic laminae, zebrafish

MeSH Terms

Animals
Animals, Genetically Modified
Retinal Ganglion Cells/chemistry
Retinal Ganglion Cells/metabolism*
Extracellular Matrix Proteins/analysis
Extracellular Matrix Proteins/biosynthesis*
Serine Endopeptidases/analysis
Serine Endopeptidases/biosynthesis*
Synapses/chemistry
Synapses/metabolism*
Nerve Net/chemistry
Nerve Net/metabolism*
Visual Pathways/chemistry
Visual Pathways/metabolism*
Nerve Tissue Proteins/analysis
Nerve Tissue Proteins/biosynthesis*
Zebrafish
Cell Adhesion Molecules, Neuronal/analysis
Cell Adhesion Molecules, Neuronal/biosynthesis*

(all 19)

PubMed

29429939 Full text @ Neuron

Abstract

A conserved organizational and functional principle of neural networks is the segregation of axon-dendritic synaptic connections into laminae. Here we report that targeting of synaptic laminae by retinal ganglion cell (RGC) arbors in the vertebrate visual system is regulated by a signaling system relying on target-derived Reelin and VLDLR/Dab1a on the projecting neurons. Furthermore, we find that Reelin is distributed as a gradient on the target tissue and stabilized by heparan sulfate proteoglycans (HSPGs) in the extracellular matrix (ECM). Through genetic manipulations, we show that this Reelin gradient is important for laminar targeting and that it is attractive for RGC axons. Finally, we suggest a comprehensive model of synaptic lamina formation in which attractive Reelin counter-balances repulsive Slit1, thereby guiding RGC axons toward single synaptic laminae. We establish a mechanism that may represent a general principle for neural network assembly in vertebrate species and across different brain areas.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
dab1a	WT	standard conditions	Protruding-mouth	periventricular grey zone neuron	ISH	Fig. S3
dab1a	WT	standard conditions	Protruding-mouth	retinal ganglion cell layer	ISH	Fig. S2
dab1b	WT	standard conditions	Protruding-mouth	amacrine cell	ISH	Fig. S2
dab1b	WT	standard conditions	Protruding-mouth	periventricular grey zone neuron	ISH	Fig. S3
GFP	dab1a^{ic3031/ic3031}; s356tTg	standard conditions	Day 5	retinal ganglion cell axon	IHC	Fig. 6
GFP	dab1a^{ic3031/ic3031}; s356tTg	standard conditions	Day 5	tectal neuropile	IHC	Fig. 6
GFP	reln^{ic3032/ic3032}; s356tTg	standard conditions	Day 5	retinal ganglion cell axon	IHC	Fig. 6
GFP	reln^{ic3032/ic3032}; s356tTg	standard conditions	Day 5	tectal neuropile	IHC	Fig. 6
GFP	s1156tEt; s356tTg; tpl2Tg	standard conditions	Day 5	retinal ganglion cell axon	IFL	Fig. 1
GFP	s318tTg + MO1-reln	standard conditions	Day 5	retinal ganglion cell axon	IHC	Fig. S1

1 - 10 of 29

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
dab1a^{ic3031/ic3031}; s356tTg	standard conditions	Day 5	retinal ganglion cell neuron projection mislocalised, abnormal	Fig. 6
ext2^{to273b/to273b}	standard conditions	Day 5	tectal neuropile reln expression decreased amount, abnormal	Fig. 4
reln^{ic3032/ic3032}	standard conditions	Day 5	tectal neuropile reln expression decreased amount, abnormal	Fig. S4
reln^{ic3032/ic3032}; s356tTg	standard conditions	Day 5	retinal ganglion cell neuron projection mislocalised, abnormal	Fig. 6
s318tTg + MO1-reln	standard conditions	Day 5	retinal ganglion cell neuron projection mislocalised, abnormal	Fig. S1
vldlr^{ic3030/ic3030}; s356tTg	standard conditions	Day 5	retinal ganglion cell neuron projection mislocalised, abnormal	Fig. 6

1 - 6 of 6

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ic3025Tg	Tg(isl2b:GAL4,myl7:EGFP)	Transgenic Insertion
ic3027Tg	Tg(rpl5b:GAL4)	Transgenic Insertion
ic3030		Insertion	vldlr
ic3031		Small Deletion	dab1a
ic3032		Indel	reln
s318tTg	Tg(pou4f3:GAL4,UAS:GAP-GFP)	Transgenic Insertion
s356tTg	Tg(pou4f3:GAP-GFP)	Transgenic Insertion
s510		Point Mutation	col4a5
s1156tEt	Et(-1.5hsp70l:GAL4-VP16)	Transgenic Insertion
to273b		MNV	ext2

1 - 10 of 11

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
dab1a	CRISPR1-dab1a	CRISPR
reln	MO1-reln	MRPHLNO
reln	TALEN1-reln	TALEN
vldlr	CRISPR1-vldlr	CRISPR

Fish

Fish
col4a5^s510/s510
dab1a^{ic3031/ic3031}; s356tTg
ext2^{to273b/to273b}
reln^{ic3032/ic3032}
reln^{ic3032/ic3032}; s356tTg
s318tTg + MO1-reln
s356tTg
s1156tEt; s356tTg; tpl2Tg
vldlr^{ic3030/ic3030}; s356tTg
WT

1 - 10 of 10

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Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-reln	monoclonal	reln	IgG1	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GAL4	EFG	GAL4
GFP	EFG	GFP
mRFP	EFG	mRFP

Mapping

Di Donato et al., 2018 ZDB-PUB-180214-4 PMID:29429939

An Attractive Reelin Gradient Establishes Synaptic Lamination in the Vertebrate Visual System

Di Donato et al., 2018

ZDB-PUB-180214-4
PMID:29429939