PUBLICATION

Gsx2 is required for specification of neurons in the inferior olivary nuclei from Ptf1a-expressing neural progenitors in zebrafish

Authors

Itoh, T., Takeuchi, M., Sakagami, M., Asakawa, K., Sumiyama, K., Kawakami, K., Shimizu, T., Hibi, M.

ID

ZDB-PUB-201002-54

Date

2020

Source

Development (Cambridge, England) 147(19): (Journal)

Registered Authors

Asakawa, Kazuhide, Hibi, Masahiko, Kawakami, Koichi, Shimizu, Takeshi, Takeuchi, Miki

Keywords

Cerebellum, Climbing fibers, Gsx2, Inferior olivary nuclei, Ptf1a, Zebrafish

MeSH Terms

Neurons/cytology*
Neurons/metabolism
Neurogenesis/genetics
Neurogenesis/physiology
Gene Expression Regulation, Developmental/genetics
Gene Expression Regulation, Developmental/physiology
Animals
Transcription Factors/genetics
Transcription Factors/metabolism
Zebrafish
Neural Stem Cells/cytology*
Neural Stem Cells/metabolism*
Homeodomain Proteins/genetics
Homeodomain Proteins/metabolism
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*

(all 16)

PubMed

32928905 Full text @ Development

Abstract

Neurons in the inferior olivary nuclei (IO neurons) send climbing fibers to Purkinje cells to elicit functions of the cerebellum. IO neurons and Purkinje cells are derived from neural progenitors expressing the proneural gene ptf1a In this study, we found that the homeobox gene gsx2 was co-expressed with ptf1a in IO progenitors in zebrafish. Both gsx2 and ptf1a zebrafish mutants showed a strong reduction or loss of IO neurons. The expression of ptf1a was not affected in gsx2 mutants and vice versa In IO progenitors, the ptf1a mutation increased apoptosis whereas the gsx2 mutation did not, suggesting that ptf1a and gsx2 are regulated independently of each other and have distinct roles. The fibroblast growth factors (Fgf) 3/8a and retinoic acid signals negatively and positively, respectively, regulated gsx2 expression and thereby the development of IO neurons. mafba and hox genes are at least partly involved in the Fgf- and retinoic acid-dependent regulation of IO neuronal development. Our results indicate that gsx2 mediates the rostro-caudal positional signals to specify the identity of IO neurons from ptf1a-expressing neural progenitors.

Genes / Markers

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
fgf8a^{ti282a/ti282a}; mafba^{nkgsaizgffm35aGt}; nkuasgfp1aTg; nns30Tg + MO5-fgf3	standard conditions	Protruding-mouth	inferior olive neuron increased amount, abnormal	Fig. 7
gsx2^nub32/nub32	standard conditions	Day 5	hindbrain apoptotic process normal occurrence, normal	Fig. 5
gsx2^nub32/nub32	standard conditions	Day 5	inferior olive neuron foxp2 expression absent, abnormal	Fig. 2
gsx2^nub32/nub32	standard conditions	Day 5	inferior olive neuron grm5a expression absent, abnormal	Fig. 2
gsx2^nub32/nub32	standard conditions	Day 5	inferior olive neuron pou4f1 expression absent, abnormal	Fig. 2
gsx2^nub32/nub32; nkhspGFFDMC28CEt; nkuasgfp1aTg	standard conditions	Day 5	inferior olive neuron decreased amount, abnormal	Fig. 2
gsx2^nub32/nub32; nkmnGFF7Tg; nkuasgfp1aTg	standard conditions	Day 5	hindbrain posterior side has fewer parts of type neuron, abnormal	Fig. 2
gsx2^nub32/nub32; nkmnGFF7Tg; nkuasgfp1aTg	standard conditions	Day 5	inferior olive neuron decreased amount, abnormal	Fig. 2
jh16Tg; nub37Tg	standard conditions	Protruding-mouth	inferior olive neuron normal amount, normal	Fig. 6
mafba^b337/b337; nkhspGFFDMC28CEt; nkuasgfp1aTg	standard conditions	Day 5	inferior olive neuron increased amount, abnormal	Fig. 8

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
b337		Point Mutation	mafba
jh1Tg	Tg(ptf1a:EGFP)	Transgenic Insertion
jh16Tg	TgBAC(ptf1a:GAL4-VP16)	Transgenic Insertion
nkgsaizgffm35aGt	Gt(gSAIz-GAL4FFM)	Transgenic Insertion	mafba
nkhspGFFDMC28CEt	Et(hsp70l:GAL4FFDMC)	Transgenic Insertion
nkmnGFF7Tg	TgBAC(mnx2b:GAL4FF)	Transgenic Insertion
nkuasgfp1aTg	Tg(5xUAS:EGFP)	Transgenic Insertion
nns30Tg	TgBAC(gsx2:LOXP-Tomato-LOXP-GFP)	Transgenic Insertion
nub32		Small Deletion	gsx2
nub33		Small Deletion	gsx2

1 - 10 of 14

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
aldh1a2	MO2-aldh1a2	MRPHLNO
fgf3	MO5-fgf3	MRPHLNO
gsx2	CRISPR1-gsx2	CRISPR
gsx2	CRISPR2-gsx2	CRISPR
pbx2	MO1-pbx2	MRPHLNO
pbx4	MO2-pbx4	MRPHLNO
pbx4	MO3-pbx4	MRPHLNO
ptf1a	CRISPR2-ptf1a	CRISPR
ptf1a	CRISPR3-ptf1a	CRISPR

1 - 9 of 9

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Fish

Fish
fgf8a^{ti282a/ti282a}; mafba^{nkgsaizgffm35aGt}; nkuasgfp1aTg; nns30Tg + MO5-fgf3
gsx2^nub32/nub32
gsx2^nub32/nub32; nkhspGFFDMC28CEt; nkuasgfp1aTg
gsx2^nub32/nub32; nkmnGFF7Tg; nkuasgfp1aTg
jh16Tg; nub37Tg
mafba^b337/b337; nkhspGFFDMC28CEt; nkuasgfp1aTg
mafba^{nkgsaizgffm35aGt/nkgsaizgffm35aGt}; nkuasgfp1aTg; nns30Tg
mafba^{nkgsaizgffm35aGt}; nkuasgfp1aTg; nns30Tg
mafba^{nkgsaizgffm35aGt}; nkuasgfp1aTg; nns30Tg + MO2-aldh1a2
nkhspGFFDMC28CEt; nkuasgfp1aTg

1 - 10 of 15

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GAL4	EFG	GAL4
GAL4FF	EFG	GAL4FF
GFP	EFG	GFP
mCherry	EFG	mCherry
RFP	EFG	RFP
Tomato	EFG	Tomato

Mapping

Itoh et al., 2020 ZDB-PUB-201002-54 PMID:32928905

Gsx2 is required for specification of neurons in the inferior olivary nuclei from Ptf1a-expressing neural progenitors in zebrafish

Itoh et al., 2020

ZDB-PUB-201002-54
PMID:32928905