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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.)