Metzker-Pinto Thaís, Tran Yen T H, Buzzatto-Leite Igor, Lok Lloyd, Sampar Jórdan F, Carvalho Hernandes F, Del Monte-Nieto Gonzalo, Alvares Lúcia E
Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia.
Dev Biol. 2025 May;521:96-107. doi: 10.1016/j.ydbio.2025.02.008. Epub 2025 Feb 11.
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.
WFDC1编码一种细胞外基质蛋白，该蛋白在疾病状态下参与细胞增殖、迁移和上皮-间质转化。尽管如此，Wfdc1基因敲除小鼠没有明显的畸形，而携带WFDC1突变的牛则出现多种眼部缺陷，这使得WFDC1在胚胎发育过程中的作用尚不清楚。为了解决这个问题，我们以鸡胚为模型来研究WFDC1在羊膜动物中的发育作用。我们在鸡和小鼠的发育过程中进行了比较表达分析，结果显示该基因在外胚层和中胚层衍生物中表达，具有保守和物种特异性结构域。在眼睛、耳泡、中枢和外周神经系统以及神经嵴细胞中观察到保守表达。在中胚层结构中发现了鸡特异性表达，包括脊索、四肢和心脏。然而，即使在眼睛等保守部位，WFDC1也定位于不同的视网膜层，这表明该基因在不同物种的视网膜发育和功能中可能具有不同的作用。相比之下，WFDC1在鸡胚肢芽中的表达是特异性的，包括远端间充质、趾间膜和胚芽。功能富集分析将WFDC1与肢体模式形成、形态发生和Wnt信号传导联系起来。物种特异性差异可能源于基因调控的进化变化，鸡和小鼠之间WFDC1基因座近端顺式调控元件的差异支持了这一点。WFDC1在鸡胚中表达的复杂性，以及鸟类中WFDC1调控的保守性，表明该基因可能在鸟类发育中发挥特定作用，可能促成了该谱系特有的特征。未来使用鸡模型的研究将有助于进一步揭示WFDC1的具体作用。
