Arhgef18, also known as p114RhoGEF, is a Rho guanine nucleotide exchange factor. It plays a crucial role in activating RhoA, a small GTPase protein, and is involved in multiple key biological processes. Arhgef18 is associated with pathways regulating actomyosin dynamics, cell-cell adhesion, and gene expression, which are essential for tissue and organ development [1,2,3,4]. Genetic models, such as gene knockout in animals, have been valuable in studying its functions.

In mice, Arhgef18 is required for syncytiotrophoblast differentiation and placenta development. It coordinates PKA/CREB signaling and actomyosin remodeling to promote trophoblast cell-cell fusion [1]. In medaka fish, mutations of Arhgef18 affect the apicobasal polarity of the retinal neuroepithelium. It regulates RhoA-Rock2 signaling to maintain this polarity at the onset of retinal differentiation and control the ratio of neurogenic to proliferative cell divisions [2,3]. In humans, biallelic mutations in ARHGEF18 cause adult-onset retinal degeneration, and the retinal structure in these individuals resembles that of subjects with mutations in another related gene, CRB1 [4].

In conclusion, Arhgef18 is essential for maintaining cell polarity, regulating cell-cell fusion during development, and has implications in retinal development and function. Gene knockout models in fish and mice have been instrumental in revealing these functions, highlighting its importance in understanding the mechanisms underlying placental development and retinal diseases.