PUBLICATION

Type IV Collagen Controls the Axogenesis of Cerebellar Granule Cells by Regulating Basement Membrane Integrity in Zebrafish

Authors

Takeuchi, M., Yamaguchi, S., Yonemura, S., Kakiguchi, K., Sato, Y., Higashiyama, T., Shimizu, T., Hibi, M.

ID

ZDB-PUB-151010-2

Date

2015

Source

PLoS Genetics 11: e1005587 (Journal)

Registered Authors

Hibi, Masahiko, Takeuchi, Miki

Keywords

Axons, Larvae, Collagens, Hindbrain, Retinal ganglion cell, Zebrafish, Cerebellum, Superior colliculus

MeSH Terms

Axons/metabolism
Nerve Tissue Proteins/genetics
Cerebellum/growth & development
Cerebellum/metabolism*
Animals
Collagen Type IV/genetics*
Collagen Type IV/metabolism
Zebrafish Proteins/genetics
Basement Membrane/growth & development
Basement Membrane/metabolism
Purkinje Cells/metabolism
Extracellular Matrix/genetics
Extracellular Matrix/metabolism
Zebrafish/genetics*
Zebrafish/growth & development
Retinal Ganglion Cells/metabolism*

(all 16)

PubMed

26451951 Full text @ PLoS Genet.

Abstract

Granule cells (GCs) are the major glutamatergic neurons in the cerebellum, and GC axon formation is an initial step in establishing functional cerebellar circuits. In the zebrafish cerebellum, GCs can be classified into rostromedial and caudolateral groups, according to the locations of their somata in the corresponding cerebellar lobes. The axons of the GCs in the caudolateral lobes terminate on crest cells in the dorsal hindbrain, as well as forming en passant synapses with Purkinje cells in the cerebellum. In the zebrafish mutant shiomaneki, the caudolateral GCs extend aberrant axons. Positional cloning revealed that the shiomaneki (sio) gene locus encodes Col4a6, a subunit of type IV collagen, which, in a complex with Col4a5, is a basement membrane (BM) component. Both col4a5 and col4a6 mutants displayed similar abnormalities in the axogenesis of GCs and retinal ganglion cells (RGCs). Although type IV collagen is reported to control axon targeting by regulating the concentration gradient of an axonal guidance molecule Slit, Slit overexpression did not affect the GC axons. The structure of the BM surrounding the tectum and dorsal hindbrain was disorganized in the col4a5 and col4a6 mutants. Moreover, the abnormal axogenesis of the caudolateral GCs and the RGCs was coupled with aberrant BM structures in the type IV collagen mutants. The regrowth of GC axons after experimental ablation revealed that the original and newly formed axons displayed similar branching and extension abnormalities in the col4a6 mutants. These results collectively suggest that type IV collagen controls GC axon formation by regulating the integrity of the BM, which provides axons with the correct path to their targets.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
col4a5	col4a6^rk18/rk18	standard conditions	Protruding-mouth	hindbrain dorsal region	ISH	Fig. 2
col4a5	col4a6^rk18/rk18	standard conditions	Protruding-mouth	hindbrain epidermal cell	ISH	Fig. 2
col4a5	WT	standard conditions	Protruding-mouth	hindbrain dorsal region	ISH	Fig. 2
col4a5	WT	standard conditions	Protruding-mouth	hindbrain epidermal cell	ISH	Fig. 2
col4a6	col4a6^rk18/rk18	standard conditions	Protruding-mouth	hindbrain dorsal region	ISH	Fig. 2
col4a6	col4a6^rk18/rk18	standard conditions	Protruding-mouth	hindbrain epidermal cell	ISH	Fig. 2
col4a6	WT	standard conditions	Protruding-mouth	hindbrain dorsal region	ISH	Fig. 2
col4a6	WT	standard conditions	Protruding-mouth	hindbrain epidermal cell	ISH	Fig. 2
EGFP	col4a6^rk18/rk18; nkhspGFFDMC90AEt; nkuasgfp1aTg	transection: axon: cerebellar granule cell	Days 7-13	cerebellar granule cell axon	IHC	Fig. 8
EGFP	col4a6^rk18/rk18; nkhspGFFDMC90AEt; nkuasgfp1aTg	standard conditions	Days 7-13	cerebellar granule cell axon	IHC	Fig. 8

1 - 10 of 39

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
col4a5^s510/s510; s318tTg	standard conditions	Day 5	cerebellar granule cell axon extension involved in axon guidance decreased process quality, abnormal	Fig. 3
col4a5^s510/s510; s318tTg	standard conditions	Day 5	hindbrain basement membrane ab1-lama1 labeling spatial pattern, abnormal	Fig. 5
col4a5^s510/s510; s318tTg	standard conditions	Day 5	hindbrain basement membrane irregular spatial pattern, abnormal	Fig. 5
col4a5^s510/s510; s318tTg	standard conditions	Day 5	hindbrain basement membrane organization decreased process quality, abnormal	Fig. 5
col4a5^s510/s510; s318tTg	standard conditions	Day 5	optic tectum basement membrane ab1-lama1 labeling spatial pattern, abnormal	Fig. 5
col4a5^s510/s510; s318tTg	standard conditions	Day 5	optic tectum basement membrane irregular spatial pattern, abnormal	Fig. 5
col4a5^s510/s510; s318tTg	standard conditions	Day 5	optic tectum basement membrane organization decreased process quality, abnormal	Fig. 5
col4a5^s510/s510; s318tTg	standard conditions	Day 5	retinal ganglion cell retinal ganglion cell axon guidance decreased process quality, abnormal	Fig. 3
col4a6^rk18/rk18	standard conditions	Protruding-mouth	hindbrain dorsal region col4a6 expression decreased amount, abnormal	Fig. 2
col4a6^rk18/rk18	standard conditions	Protruding-mouth	hindbrain epidermal cell col4a6 expression decreased amount, abnormal	Fig. 2

1 - 10 of 35

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
a9		Complex	mpv17
nkgSA2AzGFF152BGt	Gt(gSA2Az-GAL4FF)	Transgenic Insertion
nkgSAIGFF23CGt	Gt(IRES-GAL4FF)	Transgenic Insertion
nkhspGFFDMC90AEt	Et(hsp70l:GAL4FFDMC)	Transgenic Insertion
nkuasgfp1aTg	Tg(5xUAS:EGFP)	Transgenic Insertion
rk8Tg	Tg(UAS:Kaede)	Transgenic Insertion
rk18		Point Mutation	col4a6
rw015aTg	Tg(hsp70l:slit2-GFP)	Transgenic Insertion
s311tTg	Tg(pou4f3:GAL4)	Transgenic Insertion
s318tTg	Tg(pou4f3:GAL4,UAS:GAP-GFP)	Transgenic Insertion

1 - 10 of 12

Show

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
col4a5^s510/s510; s318tTg
col4a6^rk18/rk18
col4a6^rk18/rk18; nkhspGFFDMC90AEt; nkuasgfp1aTg
col4a6^rk18/rk18; s318tTg
nkgSA2AzGFF152BGt; rk8Tg
nkhspGFFDMC90AEt; nkuasgfp1aTg
rw015aTg
rw015aTg; s318tTg
s318tTg
WT

1 - 10 of 10

Show

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GAL4	EFG	GAL4
GAL4FF	EFG	GAL4FF
GFP	EFG	GFP
Kaede	EFG	Kaede

Mapping

Takeuchi et al., 2015 ZDB-PUB-151010-2 PMID:26451951

Type IV Collagen Controls the Axogenesis of Cerebellar Granule Cells by Regulating Basement Membrane Integrity in Zebrafish

Takeuchi et al., 2015

ZDB-PUB-151010-2
PMID:26451951