PUBLICATION

A series of no isthmus (noi) alleles of the zebrafish pax2.1 gene reveals multiple signaling events in development of the midbrain-hindbrain boundary

Authors

Lun, K. and Brand, M.

ID

ZDB-PUB-980916-3

Date

1998

Source

Development (Cambridge, England) 125: 3049-3062 (Journal)

Registered Authors

Brand, Michael, Lun, Klaus

Keywords

midbrain-hindbrain organizer; neurogenesis; regionalization; neural patterning; splicing; Pax genes; no isthmus; zebrafish; Danio rerio

MeSH Terms

DNA-Binding Proteins/genetics
DNA-Binding Proteins/physiology*
Genetic Markers/genetics
Conserved Sequence/genetics
Animals
Nuclear Proteins/genetics
Trans-Activators/genetics
Zebrafish/embryology*
Mutation/genetics
In Situ Hybridization
PAX2 Transcription Factor
RNA Splicing/genetics
PAX5 Transcription Factor
Alleles
Brain/growth & development*
Gene Expression Regulation, Developmental/genetics
Paired Box Transcription Factors
Transcription Factors/genetics
Transcription Factors/physiology*
Signal Transduction/physiology*
Zebrafish Proteins

(all 21)

PubMed

9671579 Full text @ Development

Abstract

Generation of cell diversity in the vertebrate central nervous system starts during gastrulation stages in the ectodermal germ layer and involves specialized cell groups, such as the organizer located at the midbrain-hindbrain boundary (MHB). Mutations in the zebrafish no isthmus (noi) gene alter development of the MHB, and affect the pax2.1 gene (formerly pax(zf-b)). Analysis of the structure of pax2.1 reveals at least 12 normal splice variants. The noi alleles can be arranged, by molecular and phenotypic criteria, into a series of five alleles of differing strength, ranging from a null allele to weak alleles. In keeping with a role in development of the MHB organizer, gene expression is already affected in the MHB primordium of the gastrula neural ectoderm in noi mutants. eng3 activation is completely and eng2 activation is strongly dependent on noi function. In contrast, onset of wnt1, fgf8 and her5 expression occurs normally in the null mutants, but is eliminated later on. Our observations suggest that three signaling pathways, involving pax2.1, wnt1 and fgf8, are activated independently in early anterior-posterior patterning of this area. In addition, analysis of the allelic series unexpectedly suggests that noi activity is also required during dorsal-ventral patterning of the MHB in somitogenesis stages, and possibly in a later eng expression phase. We propose that noi/pax2.1 participates in sequential signaling processes as a key integrator of midbrain-hindbrain boundary development.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
en1a	pax2a^tu29a/tu29a	standard conditions	Prim-5	Not Detected	midbrain hindbrain boundary	ISH	Fig. 8
en1a	WT	standard conditions	Prim-5		midbrain hindbrain boundary	ISH	Fig. 8
en2a	pax2a^tb21/tb21	standard conditions	5-9 somites		midbrain hindbrain boundary neural rod	ISH	Fig. 6
en2a	pax2a^{tm243a/tm243a}	standard conditions	1-4 somites		midbrain hindbrain boundary neural keel	ISH	Fig. 6
en2a	pax2a^tu29a/tu29a	standard conditions	Prim-5	Not Detected	floor plate neural tube	ISH	Fig. 8
en2a	pax2a^tu29a/tu29a	standard conditions	Prim-5		midbrain hindbrain boundary	ISH	Fig. 8
en2a	pax2a^tu29a/tu29a	standard conditions	90%-epiboly		midbrain hindbrain boundary neural plate	ISH	Fig. 6
en2a	pax2a^ty31a/ty31a	standard conditions	Prim-5		floor plate neural tube	ISH	Fig. 8
en2a	pax2a^ty31a/ty31a	standard conditions	Prim-5		midbrain hindbrain boundary	ISH	Fig. 8
en2a	WT	standard conditions	Prim-5		floor plate neural tube	ISH	Fig. 8

1 - 10 of 53

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
pax2a^tb21/tb21	standard conditions	Prim-5	cerebellum absent, abnormal	Fig. 1
pax2a^tb21/tb21	standard conditions	Prim-5	midbrain hindbrain boundary absent, abnormal	Fig. 1
pax2a^tb21/tb21	standard conditions	Prim-5	midbrain-hindbrain boundary development disrupted, abnormal	Fig. 1
pax2a^tb21/tb21	standard conditions	Prim-5	optic tectum decreased size, abnormal	Fig. 1
pax2a^tu29a/tu29a	standard conditions	Prim-5	cerebellum absent, abnormal	Fig. 1
pax2a^tu29a/tu29a	standard conditions	Prim-5	midbrain hindbrain boundary absent, abnormal	Fig. 1
pax2a^tu29a/tu29a	standard conditions	Prim-5	midbrain-hindbrain boundary development arrested, abnormal	Fig. 1
pax2a^tu29a/tu29a	standard conditions	Prim-5	optic tectum absent, abnormal	Fig. 1
pax2a^tu29a/tu29a	standard conditions	Days 7-13	gut epithelium edematous, abnormal	Fig. 1
pax2a^tu29a/tu29a	standard conditions	Days 7-13	pericardium edematous, abnormal	Fig. 1

1 - 10 of 10

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Mutations / Transgenics

Allele	Type	Affected Genomic Region
tb21	Point Mutation	pax2a
th44	Point Mutation	pax2a
tm243a	Point Mutation	pax2a
tu29a	Point Mutation	pax2a
ty22b	Point Mutation	pax2a
ty31a	Point Mutation	pax2a

1 - 6 of 6

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
pax2a^tb21/tb21
pax2a^th44/th44
pax2a^{tm243a/tm243a}
pax2a^tu29a/tu29a
pax2a^ty22b/ty22b
pax2a^ty31a/ty31a
WT

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Lun et al., 1998 ZDB-PUB-980916-3 PMID:9671579

A series of no isthmus (noi) alleles of the zebrafish pax2.1 gene reveals multiple signaling events in development of the midbrain-hindbrain boundary

Lun et al., 1998

ZDB-PUB-980916-3
PMID:9671579