Browsing by Author "Shinohara, Kyosuke"
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- Cilia at the node of mouse embryos sense fluid flow for left-right determination via Pkd2Publication . Yoshiba, Satoko; Shiratori, Hidetaka; Kuo, Ivana Y.; Kawasumi, Aiko; Shinohara, Kyosuke; Nonaka, Shigenori; Asai, Yasuko; Sasaki, Genta; Belo, José A.; Sasaki, Hiroshi; Nakai, Junichi; Dworniczak, Bernd; Ehrlich, Barbara E.; Pennekamp, Petra; Hamada, HiroshiUnidirectional fluid flow plays an essential role in the breaking of left-right (L-R) symmetry in mouse embryos, but it has remained unclear how the flow is sensed by the embryo. We report that the Ca2+ channel Polycystin-2 (Pkd2) is required specifically in the perinodal crown cells for sensing the nodal flow. Examination of mutant forms of Pkd2 shows that the ciliary localization of Pkd2 is essential for correct L-R patterning. Whereas Kif3a mutant embryos, which lack all cilia, failed to respond to an artificial flow, restoration of primary cilia in crown cells rescued the response to the flow. Our results thus suggest that nodal flow is sensed in a manner dependent on Pkd2 by the cilia of crown cells located at the edge of the node.
- Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNAPublication . Nakamura, Tetsuya; Saito, Daisuke; Kawasumi, Aiko; Shinohara, Kyosuke; Asai, Yasuko; Takaoka, Katsuyoshi; Dong, Fenglan; Takamatsu, Atsuko; A. Belo, José; Mochizuki, Atsushi; Hamada, HiroshiBreaking of left-right symmetry in mouse embryos requires fluid flow at the node, but the precise action of the flow has remained unknown. Here we show that the left-right asymmetry of Cerl2 expression around the node, a target of the flow, is determined post-transcriptionally by decay of Cerl2 mRNA in a manner dependent on its 3' untranslated region. Cerl2 mRNA is absent specifically from the apical region of crown cells on the left side of the node. Preferential decay of Cerl2 mRNA on the left is initiated by the leftward flow and further enhanced by the operation of Wnt-Cerl2 interlinked feedback loops, in which Wnt3 upregulates Wnt3 expression and promotes Cerl2 mRNA decay, whereas Cerl2 promotes Wnt degradation. Mathematical modelling and experimental data suggest that these feedback loops behave as a bistable switch that can amplify in a noise-resistant manner a small bias conferred by fluid flow.
- The dynamic right-to-left translocation of Cerl2 is involved in the regulation and termination of nodal activity in the mouse nodePublication . Inacio, Jose Manuel; Marques, Sara; Nakamura, Tetsuya; Shinohara, Kyosuke; Meno, Chikara; Hamada, Hiroshi; Belo, Jose AntonioThe determination of left-right body asymmetry in mouse embryos depends on the interplay of molecules In a highly sensitive structure, the node. Here, we show that the localization of Cerl2 protein does not correlate to its mRNA expression pattern, from 3-somite stage onwards. Instead, Cerl2 protein displays a nodal flow-dependent dynamic behavior that controls the activity of Nodal in the node, and the transmission of the laterality information to the left lateral plate mesoderm (LPM). Our results indicate that Cerl2 initially localizes and prevents the activation of Nodal genetic circuitry on the right side of the embryo, and later its right-to-left translocation shutdowns Nodal activity in the node. The consequent prolonged Nodal activity in the node by the absence of Cerl2 affects local Nodal expression and prolongs its expression in the LPM. Simultaneous genetic removal of both Nodal node inhibitors, Cerl2 and Lefty1, sustains even longer and bilateral his LPM expression.