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FLASH GENE

Symbol

FGF10

contributors: mct - updated : 31-01-2016

HGNC name	fibroblast growth factor 10
HGNC id	3666

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ALSG aplasia of lacrymal and salivary gland LADD3 lacrimo-auriculo-dento-digital syndrome 3
Location	5p12      Physical location : 44.305.096 - 44.388.784
Synonym name	keratinocyte growth factor 2
	produced by fibroblasts of urinary bladder lamina propria
Synonym symbol(s)	KGF2

DNA

TYPE	functioning gene
STRUCTURE	83.69 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

text structure

enhancer containing a highly conserved ISL1 consensus binding site within the FGF10 first intron

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004465 3 - 627 NP_004456 - 208 - 1999 9916808

EXPRESSION

Type

widely

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 intestine small intestine     highly Nervous brain limbic system hippocampus dentate gyrus highly   brain hindbrain cerebellum   highly   brain diencephalon thalamus   highly Reproductive female system ovary ovarian follicle   highly Homo sapiens Adult   female system ovary ovarian follicle     Homo sapiens Fetal

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly

cells

System Cell Pubmed Species Stage Rna symbol Reproductive epithelial cell Reproductive oocyte Homo sapiens Fetal Reproductive oocyte Homo sapiens Adult Respiratory alveolar cell type II Skin/Tegument keratinocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	mesenchymal cells, lung, limbs, embryonic pancreatic mesenchyme
	developing epidermis, hair follicle

PROTEIN

PHYSICAL PROPERTIES		Hydrophobic
STRUCTURE

motifs/domains	hydrophobic N terminal domain (40AA) serving as a signal sequence
	a FGF domain
	two N-glycosylation sites
	an heparin binding site and several phosphorylation sites

conjugated

GlycoP , RiboP

HOMOLOGY

interspecies	homolog to rattus Fgf10 (100.00 pc)
	homolog to murine Fgf10 (94.69 pc)

intraspecies

paralog to FGF7

Homologene

FAMILY

heparin-binding growth factors family

CATEGORY

signaling growth factor

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,nucleus

basic FUNCTION	initiation and growth of the limb bud
	triggering FGF8 expression in ectoderm and SHH expression in mesoderm
	regulate keratinocyte proliferation and differentiation by binding to the tyrosine kinase KGF receptor (FGFR2)
	stimulating wound healing
	essential regulator of lung and limb formation
	role in prostatic development, morphogenesis and epithelial proliferation, adipogenesis
	promoting the proliferation of embryonic pancreatic epithelial cells
	regulates the morphogenesis of the hepatopancreatic duct and intestinal tube
	regulating G1 cyclins and CDKs
	promotes invasion and outgrowth of trophoblasts and it increases SPRY2 expression, which attenuates trophoblast sprouting
	implicated in control of neurogenesis
	controls the patterning of the tracheal cartilage rings via SHH
	potentially regulating Meckel cartilage formation during early mandibular morphogenesis by controlling the cell differentiation in the lateral area of the mandibular process
	FGF3 and FGF10 are not required for specification of cardiovascular progenitors, but rather for their normal developmental coordination
	likely functional network involving BARX2, FGF10 and MMPs that plays an essential role in regulating branching morphogenesis of the ocular glands
	may contribute to human preantral follicle development.
	FGF8 and FGF10 promotes the proliferation of the cardiac progenitor cells that form the arterial pole of the heart
	FGF10 and FGF3 secreted from the forming neurohypophysis exert direct guidance effects on hypothalamic neurosecretory axons
	prevents the differentiation of distal epithelial progenitors into SOX2-expressing airway epithelial cells
	FGF7 and FGF10 are involved in the proliferation of ameloblastoma cells through the MAPK pathway
	SDC4 participates likely in amelogenesis, and FGF10 may modulate dental epithelial cell behaviors through the regulation of SDC4 expression
	regulates regional cardiomyocyte proliferation in the fetal heart, and triggers cell-cycle re-entry of adult cardiomyocytes
	neuroprotective function of FGF10 against ischemic neuronal injury
	dual role for FGF10 in cochlear development, to regulate outgrowth of the duct and subsequently as a bidirectional signal that sequentially specifies Reissner membrane and outer sulcus non-sensory domains
	involvement in breast tumorigenesis
	role of a TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in lung organogenesis

CELLULAR PROCESS	cell life, differentiation
	cell life, proliferation/growth
	nucleotide, transcription, regulation
	cell organization/biogenesis

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

signal transduction

	FGF10/FGFR2b signaling is essential for cardiac fibroblast development and growth of the myocardium
	DLX5-FGF10 signaling cascade controls cranial neural crest and myoblast interaction during oropharyngeal patterning and development

a component

INTERACTION

DNA

RNA

small molecule

protein	ligand for FGFR2 receptor
	CEBP in adipocytes
	upregulating Na, K-ATPase via thr MAPK pathway
	interacting with FGFR2B for palate development(coordinated epithelial-mesenchymal interactions are essential during the initial stages of palate development and require an FGF-SHH signaling network)
	interacting with FGFBP1
	key role for FGF3, and a secondary role for FGF10, in WNT8A expression
	interacting with cortactin (involved in keratinocyte migration promoted by both FGF7 and FGF10)
	ELAVL1 bind and control the FGF10 and TBX4 mRNAs
	BARX2 and FGF10 cooperate in the regulation of MMPs)
	ISL1 directly regulates FGF10 transcription during human cardiac outflow formation
	TBX4 and TBX5 interact with FGF10 during the process of lung growth and branching but not during tracheal/bronchial cartilage development
	inhibition of FGF10 by inflammatory signaling involves the NFKB1-dependent interactions between RELA, SP3, and the FGF10 promoter
	PBX1 directly binds to the FGF10 promoter and cooperates with MEIS and HOX proteins to transcriptionally activate FGF10
	ETV1 and EWSR1 transactivate FGF10 directly and cooperatively in response to apical ectodermal ridge (AER)-FGFs
	LHX9 expression overlaps with FGF10 expression in the developing limb bud mesenchyme
	glycoprotein that specifically binds to FGFR2 to control signaling pathways including cell differentiation, proliferation, and apoptosis
	TBX4, TBX5 are both upstream regulators of FGF10 and RSPO2, which drive the outgrowth of all four limb buds

cell & other

REGULATION

activated by

GATA3 that directly activates FGF10 in the early inner ear, and does so through a single binding site

ASSOCIATED DISORDERS

corresponding disease(s)

ALSG , LADD3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in &8764;10p100 of breast cancers and increased levels of FGF10 are highly correlated with proliferation rate of breast cancer cell lines and cancer cell invasion

Susceptibility

to chronic obstructive pulmonary disease (COPD) to lethal lung maldevelopment, including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD)spectrum

Variant & Polymorphism other	FGF10 haploinsufficiency affects lung function measures providing a model for a dosage sensitive effect of FGF10 in the development of COPD
	SNVs or CNVs involving FGF10 loci in our subjects with lethal lung maldevelopment, including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD)spectrum

Candidate gene	candidate gene in patients with anorectal malformations and exstrophy of the cloaca
Marker	FGF10 and FGF17 could be prognostic biomarkers for survivals of acute myeloid leukemia patients
Therapy target
	System Type Disorder Pubmed cardiovascular atheroma   may be a promising agent for treatment of ischemic stroke cardiovascular aquired   potential target for cardiac repair

ANIMAL & CELL MODELS

	defective terminal differentiation and hypoplasia of
	epidermis in Fgf10(-/-) mouse
	overexpression of Fgf10 in adult mice promotes cardiomyocyte but not cardiac fibroblast cell-cycle re-entry