Evl-KO Mouse

Evl, also known as Ena/VASP-like protein, is a member of the Ena/VASP family. It plays diverse roles in regulating various biological processes. EVL is involved in the regulation of cytoskeletal dynamics, as it impacts focal adhesion size, distribution, and the number of focal adhesions in endothelial cells, thus affecting vascular permeability [3]. It also participates in angiogenesis, where it regulates VEGF receptor-2 internalization and signaling, being essential for VEGF-induced angiogenesis [1]. Additionally, EVL promotes osteo-/odontogenic differentiation of dental pulp stem cells via activating the JNK signaling pathway [2].

Global or endothelial-specific deletion of EVL in mice reveals its importance in angiogenesis. Global deletion of EVL compromises the radial sprouting of the vascular plexus in mice, and endothelial-specific EVL deletion reduces the endothelial tip cell density and filopodia formation. Gene sets related to blood vessel development and angiogenesis are down-regulated in EVL-deficient P5-retinal endothelial cells. EVL deletion also impairs VEGF-induced endothelial cell proliferation and sprouting, and reduces the internalization and phosphorylation of VEGF receptor 2 and its downstream signaling via the MAPK/ERK pathway [1]. In contrast, in mouse auditory hair cells, Evl knockout shows that EVL is not essential for cuticular plate and stereocilia development, as the cuticular plate and stereocilia are unaffected, and auditory function is largely normal [4].

In conclusion, EVL is crucial in angiogenesis, cytoskeletal regulation, and the differentiation of dental pulp stem cells. The use of EVL knockout mouse models has significantly enhanced our understanding of its role in these biological processes. While it is important for angiogenesis, it is dispensable for cuticular plate and stereocilia development in mouse auditory hair cells. These findings contribute to a better understanding of the underlying mechanisms of related physiological and pathological processes.

References:

1. Zink, Joana, Frye, Maike, Frömel, Timo, Fleming, Ingrid, Benz, Peter M. 2021. EVL regulates VEGF receptor-2 internalization and signaling in developmental angiogenesis. In EMBO reports, 22, e48961. doi:10.15252/embr.201948961. https://pubmed.ncbi.nlm.nih.gov/33512764/

2. Zeng, Kangrui, Kang, Qiongyi, Li, Yutong, Cheng, Qing, Xia, Wenwei. 2023. EVL Promotes Osteo-/Odontogenic Differentiation of Dental Pulp Stem Cells via Activating JNK Signaling Pathway. In Stem cells international, 2023, 7585111. doi:10.1155/2023/7585111. https://pubmed.ncbi.nlm.nih.gov/36684389/

3. Mascarenhas, Joseph B, Gaber, Amir A, Larrinaga, Tania M, Dudek, Steven M, Garcia, Joe G N. 2021. EVL is a novel focal adhesion protein involved in the regulation of cytoskeletal dynamics and vascular permeability. In Pulmonary circulation, 11, 20458940211049002. doi:10.1177/20458940211049002. https://pubmed.ncbi.nlm.nih.gov/34631011/

4. Yan, Keji, Zhang, Haoqing, Qu, Chengli, Sun, Xiaoyang, Xu, Zhigang. 2024. EVL is not essential for cuticular plate and stereocilia development in mouse auditory hair cells. In FEBS letters, 599, 330-339. doi:10.1002/1873-3468.15021. https://pubmed.ncbi.nlm.nih.gov/39300480/