International Journal of Marine Science, 2024, Vol.14, No.4, 256-265 http://www.aquapublisher.com/index.php/ijms 262 multiple organ systems and leading to a wide range of developmental defects. For instance, defects in the intraflagellar transport protein IFT46 result in various ciliopathies, including kidney cysts, pericardial edema, and ventral axis curvature, as observed in zebrafish and mouse models, Primary cilia play crucial roles in signaling pathways such as Sonic hedgehog (Shh) and Wnt, which are essential for brain development and other organ systems. Defects in these pathways due to ciliary dysfunction can lead to severe developmental anomalies, including brain malformations and primary microcephaly (Wheway et al., 2019). Figure 2 Mutations in scospondin Lead to the Absence of the Reissner Fiber and Defects in Body Axis Formation (Adopted from Cantaut-Belarif et al., 2018) Image caption: (A) The Reissner fiber (RF) is localized in the posterior ventricles of the brain and the spinal central canal, formed by SCO-spondin secreted from the sub-commissural organ (SCO) and floor plate (FP). (B) At 72 hours post-fertilization (hpf), scospondinicm13/icm13 and scospondinicm15/icm15 mutant larvae exhibit a curled-down phenotype. (C) The proportion of curled-down phenotype over developmental time in scospondin mutant alleles is shown. (D) Immunostaining at 24 hpf and 48 hpf reveals the condition of the Reissner fiber in the spinal cord of both mutants and control groups. (E) Immunostaining of the forebrain at 48 hpf shows the presence of Reissner fiber material in scospondinicm15/icm15 mutants but not in scospondinicm13/icm13 mutants (Adopted from Cantaut-Belarif et al., 2018) 7.2 Genetic basis of ciliopathies The genetic basis of ciliopathies is highly complex, involving mutations in over 150 different genes that affect cilia structure and function. Advances in genetic analysis and whole genome sequencing (WGS) have significantly enhanced our understanding of the molecular mechanisms underlying these disorders. The 100 000 Genomes Project, for example, aims to improve diagnosis and care for individuals with rare diseases, including ciliopathies, by utilizing WGS to identify causative mutations , This project highlights the potential of large-scale genomic initiatives to uncover the genetic underpinnings of ciliopathies and pave the way for personalized medical interventions.
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