WNT7A Human
Description
Molecular Structure and Biochemical Properties
WNT7A is a cysteine-rich, lipid-modified protein with the following key features:
Structural studies reveal that WNT7A binds to Frizzled (FZD) receptors and co-receptors like WLS (Wntless) and CALR (calreticulin) for secretion and signaling . The crystal structure (PDB: 8TZO) shows a phospholipid-mediated interaction with WLS, critical for its stability and transport .
Biological Functions
WNT7A regulates diverse developmental and pathological processes:
Embryonic Development
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Guides anterior-posterior axis formation in the female reproductive tract .
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Essential for limb patterning, skeletal morphogenesis, and Müllerian duct development .
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Maintains neural stem cell self-renewal and synaptic formation in the CNS .
Adult Tissue Homeostasis
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Modulates uterine smooth muscle function and responds to sex steroid hormones .
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Inhibits interleukin-1β (IL-1β)-induced catabolic gene expression (e.g., MMP1, MMP13) in articular chondrocytes, protecting against osteoarthritis .
Disease Mechanisms
In Oncology
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Pro-Tumorigenic Effects:
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Therapeutic Targeting:
In Regenerative Medicine
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Intraarticular Wnt7a injections reduce cartilage degradation in osteoarthritis models by inhibiting MMP activity .
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Promotes myogenic stem cell engraftment and muscle regeneration via FZD7 signaling .
Therapeutic Development
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Agonists: Potential for treating OA and neurodegenerative disorders .
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Antagonists: Investigated in cancers with WNT7A overexpression (e.g., HNSCC) .
Diagnostic Biomarkers
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Reduced WNT7A mRNA and protein levels correlate with OA severity .
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WNT7A mutations serve as diagnostic markers for rare skeletal dysplasias .
Key Challenges and Future Directions
Product Specs
Product Science Overview
The WNT gene family is known for its role in the Wnt signaling pathway, which is essential for regulating cell fate, proliferation, migration, and patterning during embryonic development. WNT7A, in particular, functions as a ligand for members of the frizzled family of seven transmembrane receptors, operating within the canonical Wnt/β-catenin signaling pathway . This pathway is vital for numerous developmental processes, including dorsal-ventral patterning during limb development, skeleton development, and urogenital tract development .
WNT7A is involved in the development of the anterior-posterior axis in the female reproductive tract and plays a critical role in uterine smooth muscle patterning and maintenance of adult uterine function . Mutations in the WNT7A gene are associated with several congenital disorders, such as Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndromes . These conditions are characterized by limb malformations and other developmental abnormalities.
Research on WNT7A has shown its potential in targeting Wnt signaling to block angiogenesis and glucose uptake in brain tumors . This highlights the therapeutic potential of modulating Wnt signaling pathways in cancer treatment. Additionally, recombinant WNT7A proteins are used in various research applications to study their role in development and disease.
