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FLASH GENE
Symbol MSX1 contributors: mct/npt/pgu - updated : 11-07-2023
HGNC name msh homeobox 1
HGNC id 7391
Corresponding disease
ECTD3 ectodermal dysplasia 3, Witkop type
FTA1 familial tooth agenesis, oligodontia 1
OFC5 orofacial cleft 5
Location 4p16.2      Physical location : 4.861.391 - 4.865.658
Synonym name
  • homeobox 7
  • muscle-segment homeobox
  • msh (Drosophila) homeo box homolog 1 (formerly homeo box 7)
    • Synonym symbol(s) HOX7, HYD1, FTA, STHAG1
    DNA
    TYPE functioning gene
    STRUCTURE 4.27 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box) (TATA box)
    cytosine-phosphate-guanine/HTF
    text structure
  • MSX1 antisense has a TATA box
  • MSX1 sense has CAAT box and HTF/CpG box
  • a putative FOXE1 consensus site in its promoter region
    • MAPPING cloned Y linked Y status confirmed
    RNA
    TRANSCRIPTS type messenger
    text expression of two RNA (one sense and other antisense)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 1940 - 303 - 2007 18177186
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrinepancreas   moderately
    Lymphoid/Immunespleen   moderately
    Reproductivefemale systemplacenta  moderately
     female systemuterus  predominantly
     female systemovary  moderately
     male systemprostate  highly
    Respiratorylung   moderately
    Skin/Tegumentskin   highly
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal, pregnancy
    Text highly in dental mesenchyme during critical bud stage
  • in the epidermis, hair follicles, and fibroblasts of the developing fetal skin
    • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • helix-turn-helix, DNA binding domain
  • C-terminal region including the MH6 domain of MSX1 plays important roles not only in tooth development and palatal fusion, but also in postnatal bone formation
    • HOMOLOGY
    interspecies homolog to Drosophila muscle segment (msh) 1
    homolog to C.elegans R07B1.1
    ortholog to rattus Msx1
    ortholog to murine Msx1
    intraspecies homolog to MSX2
    Homologene
    FAMILY
  • homeodomain family of DNA binding domain family (meta HOX)
    • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • inhibiting MYOD1 expression
  • involved in epithelial-mesenchymal signaling in many organs, playing a role in limb-pattern formation
  • potential repressor function in cell cycle progression
  • RNA polymerase 2 transcription factor, involved in skeletal development
  • acting as a transcriptional repressor
  • strongly up-regulated the Delta-Notch pathway genes DLK1, NOTCH3, and HEY1
  • MSX1, MSX2 have a dual role in calvarial development
  • MSX1 and TGFB3 signaling is crucial for proper differentiation and morphogenesis of neural crest-derived cells in eye structures
  • homeodomain transcription factor that play a crucial role in limb development
  • mesenchymal expression of MSX1 and MSX2 is required for proper SHH and BMP4 signaling to specify digit number and identity
  • MSX1 and MSX2 promote meiosis initiation
  • appears to act as a modeling factor for membranous bone; it stimulates trabecular bone metabolism but limits cortical bone growth by promoting apoptosis, and concomitantly controls the collagen-based mineralization process
  • BMP4-MSX1 pathway and OSR2 control tooth organogenesis through antagonistic regulation of expression of secreted Wnt antagonists
  • appears to be a functional tumor suppressor that regulates tumorigenesis in cervical cancer by antagonizing Notch signaling
  • plays a critical role in embryonic patterning, particularly to maintain myogenic progenitor cell fate
  • MSX1 is a crucial transcriptional repressor of myogenesis and maintains myogenic precursor cells in an undifferentiated, proliferative state
  • MSX1 is indispensable for proper mandibular tip development
    • CELLULAR PROCESS cell life, differentiation
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text embryonic, skeletal development and maintenance histogenesis and organogenesis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MSX2 in mouse limb bud patterning
  • HIST1H1B for inhibition of transcription and myogenesis
  • interaction with PIAS1, but not its sumoylation, is required for MSX1 to function as an inhibitor of myoblast differentiation through repression of myogenic regulatory genes, such as MYOD
  • interaction with PAX9 (MSX1 may serve as a modulator of the PAX9 transcription factor activity, fine-tuning BMP4 expression, and regulating its own expression in a feedback loop)
  • downstream target of PHOX2B that activates the Delta-Notch pathway in neuroblastoma
  • interacting with DLX5 (MSX1/DLX5 interaction is crucial for osteogenic induction during frontal bone development)
  • interacting with FOXE1 (role of FOXE1 in controlling the expression of MSX1 and TGFB3 relevant in craniofacial development)
  • interacting with OSR2 (OSR2 acts downstream of PAX9 and patterns the mesenchymal odontogenic field through protein-protein interactions with MSX1 and PAX9 during early tooth development)
  • MSX1 binds the DKK1 promoter and inhibits DKK1 transcription
  • BMP4 signaling suppresses tooth developmental inhibitors in the tooth mesenchyme, including DKK2 and OSR2, and synergizes with MSX1 to activate mesenchymal odontogenic potential for tooth morphogenesis and sequential tooth formation
  • direct regulatory connection between the neural plate border genes, PAX7 and MSX1/2, and FOXD3, suggesting it is an immediate downstream target
  • MSX1 is among several transcription factors that are induced by epithelial BMP4 and that, in turn, are necessary for the induction and maintenance of dental mesenchymal BMP4 expression
  • . MSX1 cooperates with PKN1 to down-regulate MYF5 and, therefore, prevent the differentiation of myogenic precursor cells
  • Emerin cooperates with MSX1 to inhibit myogenesis through maintaining the nuclear periphery localization of MSX1 and MSX1's protein partners
  • key role of MSX1 in driving tooth development through the bud-to-cap transition is to control the expression of DKK2
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) FTA1 , OFC5 , ECTD3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in Wolf-Hirschhorn syndrome, cleft lip and palate
    constitutional       loss of function
    inactivation of its repressive activity may be one cause of Wormian bones, ectopic bones that are a feature of a variety of pathological conditions in which calvarial bone development is compromised
    Susceptibility to nonsyndromic orofacial clefts
    Variant & Polymorphism other allele 4 homozygous child exposed to smoking at periconception is most sensitive in developing nonsyndromic orofacial clefts
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Msx1 knck-out mouse
  • Msx1;Msx2 double mutants are characterized by the loss of derivatives of the anterior limb mesoderm which is not observed in either of the simple mutants