左右軸の決定機構

左右差を生み出すものが線毛だったという1998年のセル論文は自分には大きな驚きでしたが、その発見は突然現れたものではなく、状況証拠がありました。左右が逆転する突然変異体の原因遺伝子が軸糸ダイニン（axonemal dynein）だったという論文が1997年にでています。

  1. Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice D M Supp 1, D P Witte, S S Potter, M Brueckner　Nature 1997https://pubmed.ncbi.nlm.nih.gov/9353118/

Mechanism of Ciliary Movement || Structure of Cilia || How do Cilia Move? || Mucociliary Clearnace Nonstop Neuron チャンネル登録者数 13.9万人

How Do Cilia and Flagella Move? XVIVO Scientific Animation チャンネル登録者数 5.64万人

左右軸形成の分子機構の解明に関する全てはこの論文から始まったといえるでしょう。この論文を見たとき自分は、左右を決めるだけのことなのに、こんなややこしいことが本当に起きているのだろうかとかなり懐疑的な気分になりました。それから２０年以上が経過して、このメカニズムは揺るぎないものとなり生物学の教科書に当然のように紹介されています。

Randomization of Left–Right Asymmetry due to Loss of Nodal Cilia Generating Leftward Flow of Extraembryonic Fluid in Mice Lacking KIF3B Motor Protein Shigenori Nonaka ∙ Yosuke Tanaka ∙ Yasushi Okada ∙ Sen Takeda ∙ Akihiro Harada ∙ Yoshimitsu Kanai ∙ Mizuho Kido ∙ Nobutaka Hirokawa*　Cell Volume 95, Issue 6p829-837December 11, 1998　https://www.cell.com/cell/fulltext/S0092-8674(00)81705-5

訂正 In this paper (Cell 95[6], 829–837), we described the direction of the nodal cilia rotation as counterclockwise (Figure 6B). However, our recent analyses with higher spatiotemporal resolution revealed that the actual direction is clockwise when seen from the ventral side (above the nodal pit cells). In our previous observation with lower temporal resolution (10 frames per second), the direction of the rapid rotation (∼10 rounds per second) of the nodal cilia was misinterpreted due to the artifact caused by the strobe effect. ‥　For further details, refer to our recent paper Y. Okada et al. (Molecular Cell, 1999, in press). https://www.cell.com/cell/fulltext/S0092-8674(00)80067-7

当初は繊毛の動きを反時計回りと報告したが、それはビデオの時間解像度が悪くて逆向きに動いたようにみえただけで、もっと高速で撮影したら時計まわりだったということです。

レビュー論文

  1. Nodal Flow and the Generation of Left-Right Asymmetry Cell Volume 125, Issue 1, 7 April 2006, Pages 33-45 https://www.sciencedirect.com/science/article/pii/S009286740600300X このレビュー論文では線毛が動く様子や蛍光ビーズが左側に流れていく様子などを示したわかりやすい動画も掲載されています。

左右軸形成に関する原著論文・総説論文

  1. Molecular anatomy of emerging Xenopus left–right organizer at successive developmental stages Natalia Petri, Alexandra Vetrova, Nikoloz Tsikolia, Stanislav Kremnyov Developmental Dynamics First published: 27 June 2024 https://doi.org/10.1002/dvdy.722
  2. R-Spondin 2 governs Xenopus left-right body axis formation by establishing an FGF signaling gradient　Nature Communications  Published: 02 February 2024
  3. A dual function of FGF signaling in Xenopus left-right axis formation Isabelle Schneider, Jennifer Kreis, Axel Schweickert, Martin Blum, Philipp Vick Development 01 January 2019  https://journals.biologists.com/dev/article/doi/10.1242/dev.173575/264844/am/A-dual-function-of-FGF-signaling-in-Xenopus-left
  4. Physical limits of flow sensing in the left-right organizer　Jun 14, 2017 https://doi.org/10.7554/eLife.25078　Two hypotheses have been proposed for asymmetric flow detection. According to the chemosensing hypothesis, the directional flow establishes a LR asymmetric chemical gradient that is detected by signaling systems which leads to LR asymmetric gene expression and cell responses in the LRO (Okada et al., 2005). The mechanosensing hypothesis, on the other hand, proposes that the LRO cells can detect the mechanical effects of flow. It has been suggested that this mechanosensing is mediated by a particular type of sensory cilia that is able to trigger a local, asymmetric response of the so-called crown cells, which are located at the periphery of the node (mouse LRO) (McGrath et al., 2003; Tabin and Vogan, 2003).
  5. Cerberus–Nodal–Lefty–Pitx signaling cascade controls left–right asymmetry in amphioxus Save Related Papers Chat with paper Guang Li, Xian Liu, Chaofan Xing, +2, and Yiquan Wang PNAS March 20, 2017; 114 (14) 3684-3689 https://www.pnas.org/doi/10.1073/pnas.1620519114
  6. The Left-Right Coordinator: The Role of Vg1 in Organizing Left-Right Axis Formation Cell 3 April 1998; Volume 93, Issue 1, Pages 37-46
  7. Developmental Biology Volume 189, Issue 1, 1 September 1997, Pages 68-78 Developmental Biology Regular Article Organizer Induction Determines Left–Right Asymmetry inXenopus