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Dev Dyn
2020 Aug 26;2498:912-923. doi: 10.1002/dvdy.182.
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TRPM6 and TRPM7: Novel players in cell intercalation during vertebrate embryonic development.
Runnels LW
,
Komiya Y
.
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A common theme in organogenesis is how the final structure of organs emerge from epithelial tube structures, with the formation of the neural tube being one of the best examples. Two types of cell movements co-occur during neural tube closure involving the migration of cells toward the midline of the embryo (mediolateral intercalation or convergent extension) as well as the deep movement of cells from inside the embryo to the outside of the lateral side of the neural plate (radial intercalation). Failure of either type of cell movement will prevent neural tube closure, which can produce a range of neural tube defects (NTDs), a common congenital disease in humans. Numerous studies have identified signaling pathways that regulate mediolateral intercalation during neural tube closure. Less understood are the pathways that govern radial intercalation. Using the Xenopus laevis system, our group reported the identification of transient receptor potential (TRP) channels, TRPM6 and TRPM7, and the Mg2+ ion they conduct, as novel and key factors regulating both mediolateral and radial intercalation during neural tube closure. Here we broadly discuss tubulogenesis and cell intercalation from the perspective of neural tube closure and the respective roles of TRPM7 and TRPM6 in this critical embryonic process.
R01 GM080753 NIGMS NIH HHS , T32 GM139804 NIGMS NIH HHS , 5R03HD096365 Eunice Kennedy Shriver National Institute of Child Health and Human Development, 98 Japan Spina Bifida & Hydrocephalus Research Foundation, R03 HD096365 NICHD NIH HHS , 98 Japan Spina Bifida & Hydrocephalus Research Foundation
Tubule formation is a fundamental process of various organ development during vertebrate embryogenesis. Illustrations indicate the processes of tubule formation in gastrulation, A, neural tube closure, B, renal tubes, C, and heart tube formation, D. Despite different appearances, organs originated from simple linear tube structures. The primitive tubes ultimately form complicated structures of functional organs by elongation, bending, and thinning processes
Cell intercalation contributes to tubule elongation and thinning. A, Schematic images of mediolateral intercalation. Mediolateral intercalation occurs in neural tissue of early and late neurula (highlighted by gray in the left image). Cells in same plane intercalate each other. B, Radial intercalation mainly occurs in lateral region of neurulaembryo (highlighted by gray in the left image). Cells in deep layer intercalate into superficial layer. C, During tubule formation, both mediolateral and radial intercalation contributes to tubule elongation and thinning
TRPM7 and TRPM6 are required for neural tube formation in Xenopus. A, Knockdown of either TRPM7 or TRPM6 causes neural tube defects (NTDs). Ectopic expression of Mg2+ transporter can rescue the NTDs caused by TRPM7 depletion. B, Schematic illustration of distinct functions of TRPM7 and TRPM6 during neural tube closure. Upper images display Xenopus neurula from dorsal view. Dotted lines show the position of neural folds. While TRPM7 is expressed in neural tissue (indicated by light blue), TRPM6 is expressed in lateral plate (indicated by pink). Lower images indicate transverse section of the embryo. Blue tissue indicates ectoderm and red tissue indicates mesoderm. TRPM7 is required for mediolateral intercalation around the midline, whereas TRPM6 is required for radial intercalation in the lateral region
Schematic diagram of signal transduction, which regulates cell intercalation. Noncanonical Wnt/PCP pathway mainly regulates mediolateral intercalation (left). Radial intercalation mainly relies on cell adhesion and cellâ€matrix interaction (right). TRPM7 and TRPM6 regulate mediolateral and radial intercalation, respectively (middle). Our studies have shown that intracellular Mg2+ homeostasis is a critical factor for the regulation of cell intercalation
