dll4 delta-like 4 (Drosophila) [Danio rerio (zebrafish)] - Gene

Summary

Official Symbol: dll4provided by ZNC
Official Full Name: delta-like 4 (Drosophila)provided by ZNC
Primary source: ZFIN:ZDB-GENE-041014-73
See related: Ensembl:ENSDARG00000070425 AllianceGenome:ZFIN:ZDB-GENE-041014-73
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Danio rerio
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; Danionidae; Danioninae; Danio
Also known as: zgc:136596; si:ch211-244p18.5
Summary: Predicted to enable Notch binding activity. Involved in negative regulation of sprouting angiogenesis and negative regulation of vascular endothelial cell proliferation. Acts upstream of or within several processes, including negative regulation of blood vessel endothelial cell migration; vasculature development; and ventral spinal cord interneuron differentiation. Predicted to be located in membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Is expressed in several structures, including atrioventricular canal endocardium; brain; endothelial cell; vasculature; and xanthophore. Human ortholog(s) of this gene implicated in Adams-Oliver syndrome. Orthologous to human DLL4 (delta like canonical Notch ligand 4). [provided by Alliance of Genome Resources, Apr 2022]
Orthologs: human mouse all
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Genomic context

Location:: chromosome: 20

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCz11 (GCF_000002035.6)	20	NC_007131.7 (28245295..28254015)
105	previous assembly	GRCz10 (GCF_000002035.5)	20	NC_007131.6 (28346205..28354925)

Chromosome 20 - NC_007131.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Sequencing the Zebrafish transcriptome from a range of tissues and developmental stages Sequencing the Zebrafish transcriptome from a range of tissues and developmental stages
Description: Sequencing the Zebrafish transcriptome from a range of tissues and developmental stages
BioProject: PRJEB1986
Analysis date: Fri Dec 8 19:48:10 2017

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The regulation of DLL4 by the LDB2 complex provides a novel mechanism of DLL4 transcriptional control that may be exploited to develop therapeutics for aberrant vascular remodeling.
Title: LDB2 regulates the expression of DLL4 through the formation of oligomeric complexes in endothelial cells.
Tmem230a may have a modulatory role in vessel-network formation and growth, regulating endothelial cell number by Dll4/Notch pathway.
Title: Zebrafish Tmem230a cooperates with the Delta/Notch signaling pathway to modulate endothelial cell number in angiogenic vessels.
Thsd7a could regulate ISV angiogenesis via Notch-dll4 signaling. Thus, Thsd7a is a potent angioneurin involved in the development of both neural and vascular systems.
Title: Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway.
show that blood flow suppresses vascular Notch signalling via down-regulation of dll4
Title: Blood flow suppresses vascular Notch signalling via dll4 and is required for angiogenesis in response to hypoxic signalling.
Microinjection of miR-30 mimics into zebrafish embryos resulted in suppression of dll4 and subsequent excessive sprouting of intersegmental vessels and reduction in dorsal aorta diameter.
Title: The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis.
Notch signalling pathway mutants Ectopic filopodia were also observed on the inter-somitic vessels of Notch signalling pathway mutants. Ectopic filopodia are not due to loss of dll4.
Title: Zebrafish notch signalling pathway mutants exhibit trunk vessel patterning anomalies that are secondary to somite misregulation.
These studies imply critical roles for Dll4/Notch signaling in the formation and wiring of the lymphatic network.
Title: Role of delta-like-4/Notch in the formation and wiring of the lymphatic network in zebrafish.
Vegfc/Flt4 signalling is suppressed by Dll4 in developing zebrafish intersegmental arteries.
Title: Vegfc/Flt4 signalling is suppressed by Dll4 in developing zebrafish intersegmental arteries.
Dll4-Notch signalling acts as an angiogenic ;off' switch by making endothelial cells unresponsive to Vegf.
Title: Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis.

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General gene information

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Gene Ontology Provided by ZFIN

Function	Evidence Code	Pubs
enables Notch binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in Notch signaling pathway	TAS Traceable Author Statement more info
acts_upstream_of_or_within angiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within artery development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within blood vessel development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within blood vessel endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within blood vessel endothelial cell proliferation involved in sprouting angiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within branching involved in blood vessel morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within branching involved in blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within branching involved in lymph vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cell communication	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within dorsal aorta development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within lymphangiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within lymphangiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of blood vessel endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of sprouting angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of vascular endothelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within pelvic fin development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of angiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of sprouting angiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of vascular endothelial growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within sprouting angiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within sprouting angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within venous blood vessel development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within venous blood vessel morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within venous endothelial cell migration involved in lymph vessel development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within ventral spinal cord interneuron differentiation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within ventral spinal cord interneuron differentiation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: delta-like protein 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001079835.1 → NP_001073304.1 delta-like protein 4 precursor

See identical proteins and their annotated locations for NP_001073304.1

Status: PROVISIONAL

Source sequence(s)

BC117624

UniProtKB/TrEMBL

Q1ECY3

Related

ENSDARP00000094097.3, ENSDART00000103320.4

Conserved Domains (3) summary

cd00054
Location:433 → 468

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

pfam01414
Location:148 → 210

DSL; Delta serrate ligand

pfam07657
Location:22 → 83

MNNL; N terminus of Notch ligand