International Journal of Marine Science, 2024, Vol.14, No.5, 332-340 http://www.aquapublisher.com/index.php/ijms 333 significant reduction in the number of cilia in KV, the pronephros, and the neural floorplate, leading to phenotypes reminiscent of human ciliopathies (Dutta et al., 2015). The Hippo signaling pathway and its transcriptional co-activator Yap are essential for ciliogenesis during zebrafish kidney development. Knockdown of yap results in pronephric cysts and other ciliopathy-related abnormalities, which can be rescued by full-length yap mRNA (He et al., 2015). 2.2 Tissue-specific ciliary development Ciliary development in zebrafish is tissue-specific, with different types of cilia present in various organs. For instance, endothelial cilia are crucial for maintaining vascular integrity during development. Mutations in intraflagellar transport genes, which are essential for cilia biogenesis, lead to increased risk of developmental intracranial hemorrhage, highlighting the importance of cilia in the vasculature (Kallakuri et al., 2015). In the pronephros, cilia are essential for maintaining duct integrity and proper morphogenesis. Disruption of ciliary function in this tissue leads to pronephric cysts and disorganization of the pronephric duct. Cilia in the retina are involved in sensory functions, and their dysfunction can lead to retinal dystrophy, as observed in zebrafish models of Joubert syndrome (Rusterholz et al., 2022). 2.3 Role of signaling pathways in ciliogenesis Several signaling pathways are involved in ciliogenesis in zebrafish. The Wnt signaling pathway, both canonical and non-canonical, plays a significant role in ciliary formation. Nlz1 acts downstream of Foxj1a and Wnt8a in the canonical pathway and positively regulates Wnt11 in the non-canonical pathway to promote motile cilia formation. Prostaglandin signaling also regulates ciliogenesis by modulating intraflagellar transport. PGE2, synthesized by COX1 and COX2, binds to the EP4 receptor on the cilium, activating adenylate cyclase and cAMP signaling to promote anterograde intraflagellar transport (Jin et al., 2015). Cholesterol has been shown to be crucial for cilia biogenesis and function. Pharmacological inhibition of cholesterol synthesis in zebrafish leads to cilia dysfunction and organ malformations, suggesting that cholesterol governs critical steps of cilium extension (Maerz et al., 2019). 3 Zebrafish Models for Ciliopathies 3.1 Common ciliopathies studied in zebrafish Zebrafish have been extensively used to model various human ciliopathies due to their genetic and physiological similarities to humans. Common ciliopathies studied in zebrafish include Joubert Syndrome (JBTS), nephronophthisis, and polycystic kidney disease (PKD). Joubert Syndrome is characterized by a distinctive cerebellar and brain stem malformation known as the "Molar Tooth Sign" and is associated with a variety of other ciliopathy phenotypes such as retinal dystrophy and fibrocystic renal disease (Rusterholz et al., 2022). Nephronophthisis, another ciliopathy, leads to cystic kidney disease and has been effectively modeled in zebrafish to study the function of related genes (Molinari et al., 2018). Polycystic kidney disease, characterized by the formation of fluid-filled cysts in the kidneys, has also been modeled in zebrafish, providing insights into the disease's progression and potential therapeutic strategies (Zhu et al., 2021). 3.2 Genetic manipulation to model ciliary defects Genetic manipulation in zebrafish has been pivotal in modeling ciliary defects. Techniques such as morpholino oligonucleotide (MO) injections and CRISPR/Cas9 genome editing have been employed to knock down or mutate genes associated with ciliopathies. For instance, the IFT46 gene, essential for cilium formation and maintenance, has been manipulated in zebrafish to create transgenic lines that exhibit ciliopathy-like phenotypes, including cystic kidneys and pericardial edema (Lee et al., 2023; Wang et al., 2024). TALEN technology has been used to generate tmem67 mutants, which model Meckel syndrome type 3 (MKS3) and exhibit renal cysts and ciliary abnormalities. These genetic tools allow for precise control over gene expression and the study of specific ciliary defects in zebrafish. 3.3 Phenotypic analysis of ciliopathies in zebrafish Phenotypic analysis of zebrafish models of ciliopathies involves detailed observation of ciliary structure and function, as well as the associated physiological abnormalities. For example, zebrafish models of Joubert
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