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FLASH GENE

Symbol

NODAL

contributors: mct - updated : 22-11-2016

HGNC name	nodal homolog (mouse)
HGNC id	7865

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue       Endocrine pancreas         Homo sapiens Nervous brain

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Homo sapiens Reproductive germ cell Homo sapiens

cell lineage
cell lines
fluid/secretion	amniotic fluid-derived stem cells (AFSc) seem to express NODAL, NANOG and DAZL and it speculated that the regulation of self-renewal in AFSc could be similar as in human embryonic stem cells

at STAGE

physiological period

embryo

Text	expressed in the node during gastrulation, mesoderm formation and subsequent organization of axial structures (in mouse), left side expression pattern

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

interspecies

homolog to murine Nodal

Homologene

FAMILY

TGF-beta superfamily

CATEGORY

regulatory , signaling growth factor

SUBCELLULAR LOCALIZATION

extracellular

basic FUNCTION	embryonic regulator involved in the control of the TGFD beta signaling pathway during developement,
	involved in the direction of cardiac looping
	having a key role in melanoma cell plasticity and tumorigenicity, thereby providing a molecular target for regulating tumor progression
	play a key role in specification and patterning of vertebrate embryos
	implicated in the establishment of the Antero–Posterior axis and generation of mesoderm and definitive endoderm
	not only crucial in cell invasion, but also mediates multi-potent, plastic phenotypes and other stem cell-like properties in human melanoma
	suppress cell proliferation and to stimulate the expression of cyclin G2 (CCNG2) in epithelial ovarian cancer cells
	NODAL signaling promotes CCNG2 transcription by upregulating FOXO3 expression, inhibiting FOXO3 phosphorylation and enhancing its synergistic interaction with Smads
	NBL1 might act synergistically with NODAL
	NODAL signaling provides a molecular control mechanism that regulates male germ cell potency in normal development and testicular cancer
	endogenous NODAL signaling regulates germ cell potency during mammalian testis development
	during development, NODAL depends on growth and differentiation factor GDF1 and on the shared co-receptor CFC1 to specify visceral left-right axis asymmetry
	is an essential embryonic morphogen that is associated with progression of breast and other cancers
	plays likely a regulatory role in Sertoli cells and germ cells via a paracrine and autocrine pathway, respectively
	NODAL produced by human male germ cells regulates proliferation and numerous gene expression of Sertoli cells

CELLULAR PROCESS

cell organization/biogenesis

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

signal transduction

	activin/nodal signaling pathway (inhibition of activin/nodal signaling results in the loss of hESC (embryonic stem cells) pluripotency and trophoblast differentiation, similar to BMP4-induced trophoblast differentiation from hESCs)
	CITED2 plays a role in left–right patterning through the NODAL-PITX2C pathway
	signaling by the TGFB1 morphogen NODAL and its co-receptor TDGF1 is active during a crucial window of male germ cell development
	NODAL signaling promotes male germ cell fate and suppresses female programming in somatic cells

a component

central component with EBAF, LEFTYB, PITX2 of the left-right asymetry determination (L/R) complex

INTERACTION

DNA

RNA

small molecule

protein	inducing LEFTYB
	signaling via MADH2 through binding with activin receptor ACVR1C
	interacting with Cripto (TDGF1)
	interacting with GDF1 (regulates the activity and signaling range of NODAL through direct interaction)
	TGIF1, TGIF2 function is required for gastrulation, and provide the first clear evidence that Tgifs limit the transcriptional response to NODAL signaling during early embryogenesis
	CITED2 may interact with both NODAL and BMP signalling in establishing laterality
	NODAL signaling regulates endodermal cell motility and actin dynamics via RAC1 and PREX1
	transient inhibition of NODAL by CER1 induces Brahma-associated factor 60c (SMARCD3)
	NANOG promotes liver cancer cell invasion by inducing epithelial-mesenchymal transition through NODAL/SMAD3 signaling pathway
	NODAL·GDF1 heterodimers with bound prodomains enable serum-independent nodal signaling and endoderm differentiation
	secreted antagonists, such as CER1, tightly regulate NODAL signaling during embryonic development
	FOXA2 can be a regulator of NODAL expression
	MSX2 controls mesendoderm lineage commitment by simultaneous suppression of SOX2 and induction of NODAL expression through direct binding and activation of the NODAL promoter
	TGIF1 and TGIF2 regulate the TGFB1/NODAL signaling pathway and sonic hedgehog (SHH) signaling independently

cell & other

REGULATION

Other	antagonized by EBAF, LEFTYB
	NODAL signaling pathway is activated in both male germ cells and somatic cells

ASSOCIATED DISORDERS

corresponding disease(s)

HTX5

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in metastatic melanomas constitutional germinal mutation       cause sporadic left–right (LR) patterning defects constitutional       loss of function reductions in the biological activity of NODAL alleles in congenital heart defects tumoral     --over   expression levels are significantly higher in astrocytomas, glioblastomas, oligodendrogliomas, and in malignant glioma cells compared with non-tumor tissues tumoral     --over   correlated with reduced patient survival in pancreatic cancer constitutional     --low   decreased expression of NODAL combined with haploinsufficiency for FOXA2 is the likely cause for heterotaxy, panhypopituitarism, and biliary atresia in a family (pMID: 25765999)

Susceptibility

to congenital heart disease (CHD)

Variant & Polymorphism other	contribution to CHD of copy number changes in NODAL

Candidate gene
Marker
Therapy target	inhibition of Nodal signaling may be considered as a novel therapeutic strategy in glioma treatment

ANIMAL & CELL MODELS