International Journal of Marine Science, 2024, Vol.14, No.4, 256-265 http://www.aquapublisher.com/index.php/ijms 259 axis, morphogens such as Wnt, FGF, and RA play significant roles. The inhibition of Wnt and BMP signals is necessary for the formation of anterior neural tissue, while gradients of Wnt, FGF, and RA pattern the posterior regions (Carron and Shi, 2016; Takebayashi-Suzuki and Suzuki, 2020), The interplay between these morphogens and their antagonists, such as Chordin and Noggin, further refines the patterning process, ensuring precise spatial and temporal gene expression (Bier and Robertis, 2015; Tingler et al., 2022). 3.3 Gene expression patterns The establishment of body axes is closely linked to the regulation of gene expression patterns. The expression of Hox genes, which are regulated by morphogen gradients, is crucial for AP patterning. These genes exhibit collinear expression patterns that correspond to their positions along the body axis, with early expressed Hox genes defining anterior regions and later expressed genes defining posterior regions (Carron and Shi, 2016; Durston et al., 2019), Additionally, the expression of transcription factors such as Pitx2 and Southpaw is essential for left-right (LR) axis determination, with their asymmetric expression being regulated by cilia-driven fluid flow and signaling pathways like PCP and JNK (Derrick et al., 2022; Tingler et al., 2022), The precise regulation of these gene expression patterns ensures the correct development of the vertebrate body plan. 4 Cilia and Left-Right Axis Development 4.1 Role of cilia in left-right asymmetry Cilia play a pivotal role in establishing left-right (L-R) asymmetry during embryonic development. The initial breaking of L-R symmetry is controlled by motile cilia that generate a leftward fluid flow within the left-right organizer (LRO) (Little and Norris, 2020; Hamada, 2020), This cilia-driven flow is crucial for the asymmetric expression of genes such as Nodal, which is restricted to the left side of the lateral plate mesoderm (LPM) (Grimes et al., 2016; Grimes and Burdine, 2017). In vertebrates, this process is essential for the correct positioning and morphogenesis of internal organs (Hamada, 2020). 4.2 Mechanisms of left-right patterning The mechanisms underlying L-R patterning involve a complex interplay of genetic and cellular processes. The motile cilia in the LRO create a directional fluid flow that is detected by crown cells, which in turn activate the Nodal signaling pathway on the left side (Grimes et al., 2016), This asymmetric gene expression is further propagated by the Nodal-Pitx2 pathway, which influences lateralized cell differentiation and organogenesis (Grimes and Burdine, 2017; Hamada, 2020), Additionally, planar cell polarity (PCP) signaling and the JNK gene family have been implicated in the proper functioning and orientation of nodal cilia, further contributing to L-R asymmetry (Derrick et al., 2022). 4.3 Key genes and proteins 4.3.1 Nodal signaling Nodal signaling is a critical determinant of L-R asymmetry. The asymmetric expression of Nodal in the LPM is initiated by cilia-driven fluid flow and is essential for the subsequent activation of downstream targets such as Pitx2 (Grimes and Burdine, 2017; Hamada, 2020), Nodal signaling is tightly regulated to ensure it is restricted to the left side, a process that involves various genetic interactions, including those with the polycystin-encoding genes PKD1L1 and PKD2 (Grimes et al., 2016). 4.3.2 Lefty and Pitx2 Lefty and Pitx2 are key downstream effectors of the Nodal signaling pathway. Lefty acts as a feedback inhibitor to restrict the range of Nodal signaling, ensuring that it remains confined to the left side (Grimes and Burdine, 2017). Pitx2, on the other hand, is a transcription factor that mediates the effects of Nodal signaling, driving the asymmetric development of organs (Grimes and Burdine, 2017; Hamada, 2020), The precise regulation of these genes is crucial for the correct establishment of L-R asymmetry. 4.3.3 Dynein and kinesin motor proteins Dynein and kinesin motor proteins are essential for the function and movement of cilia. Dynein, in particular, is involved in the generation of ciliary movement, which is necessary for the creation of the leftward fluid flow in
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