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WFDC1 encodes an extracellular matrix protein involved in cell proliferation, migration, and epithelial-mesenchymal transition in disease conditions. Despite this, Wfdc1-null mice display no discernible malformations while cattle bearing a WFDC1 mutation present multiple ocular defects, leaving the role of WFDC1 during embryonic development unclear. To address this, we used the chicken embryo as a model to investigate WFDC1 developmental roles in amniotes. We performed a comparative expression analysis during chicken and mouse development, which revealed expression in ectodermal and mesodermal derivatives, with both conserved and species-specific domains. Conserved expression was observed in the eye, otic vesicle, central and peripheral nervous systems, and neural crest cells. Chicken-specific expression was identified in mesodermal structures, including the notochord, limbs and heart. However, even in the conserved sites like the eyes, WFDC1 localizes to different retinal layers, indicating potential divergence roles in retinal development and function across species. In contrast, WFDC1 expression in the limb buds is specific to chicken, encompassing the distal mesenchyme, interdigital membranes, and blastemas. Functional enrichment analysis links WFDC1 to limb patterning, morphogenesis, and Wnt signaling. The species-specific differences likely stem from evolutionary changes in gene regulation, supported by differences in proximal cis-regulatory elements of the WFDC1 loci between chicken and mouse. The complexity of WFDC1 expression in the chicken embryo, along with WFDC1 regulatory conservation within birds, indicates that this gene may play specific roles in avian development, possibly contributing to features specific to this lineage. Future studies using the chicken model will be valuable in further uncovering the specific roles of WFDC1., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2025 Elsevier Inc. All rights reserved.)

PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. However, the functional role of PAX2 in ovarian cancer is not known. Twenty-six ovarian cancer cell lines with different histology origins were screened for PAX2 expression. Two ovarian cancer cell lines: RMUGL (mucinous) and TOV21G (clear cell), with high PAX2 expression were chosen for further study. Knockdown PAX2 expression in these cell lines was achieved by lentiviral shRNAs targeting the PAX2 gene. PAX2 stable knockdown cells were characterized for cell proliferation, migration, apoptosis, protein profiles, and gene expression profiles. The result indicated that these stable PAX2 knockdown cells had reduced cell proliferation and migration. Microarray analysis indicated that several genes involved in growth inhibition and motility, such as G0S2, GREM1, and WFDC1, were up-regulated in PAX2 knockdown cells. On the other hand, over-expressing PAX2 in PAX2-negative ovarian cell lines suppressed their cell proliferation. In summary, PAX2 could have both oncogenic and tumor suppression functions, which might depend on the genetic content of the ovarian cancer cells. Further investigation of PAX2 in tumor suppression and mortality is warranted. [ABSTRACT FROM AUTHOR]

Abstract: The whey acidic protein family member, WFDC1/ps20 is a permissivity factor in HIV infection. Herein we describe a contrasting role for ps20 in limiting MHV-1 infection. Intranasal MHV-1 infection produces a respiratory infection in mice. Using ps20 knockout mice we provide evidence that intranasal MHV-1 infection results in increased lung viral titers in ps20−/− compared to ps20+/+ mice. Accompanying MHV-1 infection we observe an increase in the number of neutrophils infiltrating the BAL and an increase in the percentage of neutrophils in the lung draining lymph nodes of ps20−/− compared with ps20+/+ mice. Gene expression levels for the neutrophil chemoattractants CXCL1 and CXCL2 are elevated in the lungs of ps20−/− mice post-MHV-1 infection. Characterization of the immune cell profile in naïve ps20−/− mice revealed an increase in circulating neutrophils compared to ps20+/+ mice. No notable differences in other immune cell profiles were observed between the ps20+/+ and ps20−/− mice. Accordingly, we examined MHV-1 infection of neutrophils and provide evidence that neutrophils isolated from ps20−/− mice are more susceptible to MHV-1 infection than neutrophils isolated from ps20+/+ mice. These data suggest roles for ps20 in regulating expression of neutrophil-specific chemotactic factors, thereby potentially modulating neutrophil migration, and in modulating neutrophil susceptibility to MHV-1 infection. [Copyright &y& Elsevier]

The exact cellular and molecular mechanisms involved in melanoma tumorigenesis remain obscure. Previous gene expression profiling analyses performed upon NHEM and human melanoma samples identified WFDC1 as one of the most frequently down-regulated genes. Here we further showed that NHEM readily express WFDC1 but expression is reduced or completely lost in 80% of the patients-derived melanoma cell lines and tissue samples examined. Furthermore, we show that promoter hypermethylation accounts for the silencing of the WFDC1 gene in 20% of the melanoma cell lines examined. The over-expression of WFDC1 in two metastatic melanoma cell lines, A375 and LOX, resulted in a significant delay of tumor growth in a murine xenograft model, despite a non-significant difference in tumor cell growth in vitro. Gene expression microarray analysis and further expression validation suggests that the Dickkopf-1 (Dkk1) gene is up-regulated in WFDC1 over-expressing cell lines, suggesting that the tumor suppressive function of WFDC1 may be partially a result of up-regulated Dkk1 gene expression, which is known to be a potent inhibitor of the Wnt signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: Multiple ocular defects (MOD) in cattle is an autosomal recessive hereditary disorder characterized by dysplasia of the lens, retinal detachment, persistence of the hyaloid artery, and microphthalmia. The locus responsible for MOD has been mapped to the proximal region of bovine chromosome 18. In the present study, we refined the localization of the MOD locus to a 1.0-Mb interval by haplotype analysis using a pedigree of affected animals. Comparison of nucleotide sequence of genes in this region revealed a one-nucleotide insertion in the WFDC1 gene, which resulted in a frame shift mutation and premature termination codon at the middle of the protein. WFDC1 is a small secretory protein containing a WAP-type four disulfide core domain. Specific expression of Wfdc1 was observed in the lens, retina, and optic nerves of embryonic and adult mouse eyes by immunohistochemical staining and in situ hybridization. The present finding demonstrated the essential role of WFDC1 in mammalian eye development. [Copyright &y& Elsevier]