Fire together, wire togetherという言葉が有名です。あるシナプスに関して伝達効率が上昇するかどうかを決めるのは何かと言うと、そのシナプスでのEPSPの発生したタイミングと、ポストシナプス細胞での活動電位発生のタイミングとの関係だというものです。EPSP発生直後に活動電位が発生した場合には、そのシナプスは活動電位の発生に貢献したといえ、シナプスの伝達効率が上昇します。逆に活動電位が発生した直後にそのEPSPが発生していたら、それは無関係だったということでシナプスの伝達効率が減少します。
“Basic FGF” (bFGF), or FGF2, is one specific member of the fibroblast growth factor (FGF) family. The term “FGF” is a broader designation that encompasses a family of related proteins involved in various cellular processes, including cell growth, differentiation, wound healing, and angiogenesis.
Here’s a breakdown of the distinction:
FGF (Fibroblast Growth Factors):
This is a family of growth factors with 22 known members in humans, each with unique roles and specificities. They are designated by numbers (e.g., FGF1, FGF2, FGF3, etc.).
FGFs are essential for developmental processes, tissue repair, and other physiological functions.
Basic FGF (bFGF or FGF2):
FGF2 is a particular type of FGF known for its role in promoting angiogenesis (formation of new blood vessels), wound healing, and supporting the growth of fibroblasts.
It is termed “basic” because of its relatively high isoelectric point, distinguishing it from “acidic FGF” (aFGF or FGF1), which has a lower isoelectric point.
In summary, “basic FGF” or FGF2 refers specifically to one member of the FGF family with particular biological functions and properties, while “FGF” refers to the entire family of fibroblast growth factors.
Mesendoderm (ME) refers to the primitive streak in mammalian embryos, which has the ability to further differentiate into mesoderm and endoderm.
Signaling Control of Differentiation of Embryonic Stem Cells toward Mesendoderm ALu Wang , Ye-Guang Chen Journal of Molecular Biology Volume 428, Issue 7, 10 April 2016, Pages 1409-1422 Journal home page for Journal of Molecular Biology Review https://www.sciencedirect.com/science/article/abs/pii/S0022283615003538 本文有料
Mesoendodermの分子マーカー
Existence of mesendoderm that can give rise to both endoderm and mesoderm has been reported from C. elegans to Xenopus(Rodaway and Patient, 2001). In early zebrafish development, the marginal zone bordering on the vegetal margin contains precursors for endoderm as well as mesoderm. Both brachyury and Gata5, which are specific markers for mesoderm and endoderm precursors, respectively, are co-expressed in this marginal zone(Rodaway et al., 1999).
01 October 2005 Characterization of mesendoderm: a diverging point of the definitive endoderm and mesoderm in embryonic stem cell differentiation culture Shinsuke Tada, Takumi Era, Chikara Furusawa, Hidetoshi Sakurai, Satomi Nishikawa, Masaki Kinoshita, Kazuki Nakao, Tsutomu Chiba, Shin-Ichi Nishikawa
Fig. 6. Siamois and Twin function redundantly in axial development and organizer formation.
Dev Biol. 2011 Feb 3;352(2):367–381. doi: 10.1016/j.ydbio.2011.01.034 Siamois and Twin are redundant and essential in formation of the Spemann organizer Sangwoo Bae a,b,c, Christine D Reid a,c, Daniel S Kessler a,* https://pmc.ncbi.nlm.nih.gov/articles/PMC3065516/
FGF signaling has also been shown to inhibit BMP signaling in the early embryo by several mechanisms, thus potentially influencing the response of tissue to the activity of the BMP inhibitors produced by the organizer during neural induction. FGF signaling, for example, can promote phosphorylation of the linker domain and degradation of SMAD1, thereby reducing the efficacy of BMP signaling43. FGF signaling can also inhibit BMP activity indirectly, by inducing the expression of a protein called Zeb2, a zinc-finger homeodomain protein also known as SIP1 (and Zfhx1b), which binds to and represses the transcriptional activity of the SMAD protein44. For much of the neural plate, the role of FGF signaling is likely to be minor, since neural induction by the BMP inhibitors occurs readily in Xenopus in the absence of FGF signaling45.
Neural induction and early patterning in vertebrates Mohammad Zeeshan Ozair 1, Chris Kintner 2, Ali H Brivanlou 1,* Wiley Interdiscip Rev Dev Biol. 2012 Oct 15;2(4):479–498. doi: 10.1002/wdev.90 https://pmc.ncbi.nlm.nih.gov/articles/PMC6945772/
Gilbert Developmental Biology FIGURE 12.21 noggin mRNAインジェクションによるUV腹側化胚の背側構造レスキュー（A)、内在性noggin mRNAの局在（B)。(B) Localization of noggin mRNA in the organizer tissue, shown by in situ hybridization. At gastrulation (i and ii, stage 9), noggin mRNA (dark areas) accumulates in the dorsal marginal zone. When cells involute (i and iii, stages 9 and 10), noggin mRNA is seen in the dorsal blastopore lip. During convergent extension (iii, stage 10), noggin is expressed in the precursors of the notochord, prechordal plate, and pharyngeal endoderm, which in the neurula (iv, v) extend beneath the ectoderm in the center of the embryo. Barresi, Michael; Gilbert, Scott. Developmental Biology XE (English Edition) (p.3663). Sinauer Associates is an imprint of Oxford University Press. Kindle 版.
TGFß signals belonging to the Nodal family set up the embryonic axes, induce mesoderm and endoderm, pattern the nervous system, and determine left-right asymmetry in vertebrates.
Annual Review of Cell and Developmental Biology Volume 19, 2003 Review Article Nodal Signaling in Vertebrate Development Alexander F. Schierhttps://www.annualreviews.org/content/journals/10.1146/annurev.cellbio.19.041603.094522 本文有料
Nodal-related 1 (ndr1) and nodal-related 2 (ndr2)genes in zebrafish encode members of the nodal subgroup of the transforming growth factor-β superfamily. We report the expression patterns and functional characteristics of these factors, implicating them in the establishment of dorsal–ventral polarity and left–right asymmetry.
Zebrafish Nodal-Related Genes Are Implicated in Axial Patterning and Establishing Left–Right Asymmetry Michael R. Rebagliati a , Reiko Toyama a , Cornelia Fricke b , Pascal Haffter b , Igor B. Developmental Biology Volume 199, Issue 2, 15 July 1998, Pages 261-272 Dawid https://www.sciencedirect.com/science/article/pii/S0012160698989357?via%3Dihub
Follow your gut: Relaying information from the site of left–right symmetry breaking in the mouse Yukio Saijoh, Manuel Viotti, Anna-Katerina Hadjantonakis First published: 19 April 2014 https://doi.org/10.1002/dvg.22783
Snail family genes are required for left–right asymmetry determination, but not neural crest formation, in mice Stephen A. Murray and Thomas Gridley tom.gridley@jax.orgAuthors Info & Affiliations Edited by Kathryn V. Anderson, Sloan–Kettering Institute, New York, NY, and approved May 26, 2006 July 5, 2006 103 (27) 10300-10304 PNAS https://www.pnas.org/doi/10.1073/pnas.0602234103
Nodalの神経誘導作用
下の論文の図のd Control k81（表皮のマーカー）、sox2（神経板のマーカー）を見ると、外胚葉が表皮と神経板とに分化した様子が見事にわかります。非常に興味深いのはNodalを胞胚腔に注入した胚における神経板の広がりです。表皮の部分が狭まり、その分、神経板が大きく広がっています。つまり、Nodalは強力な神経誘導作用を持つと言えます。ただし、直接的な作用なのか、間接的な作用（誘導因子を誘導して）なのかの区別がメカニズムを考えるうえで重要になります。タンパク質を胞胚腔に顕微注入しているので、内胚葉、中胚葉、外胚葉全てに作用しうる実験条件だと思います。
Nodal/Activin Pathway is a Conserved Neural Induction Signal in Chordates Nat Ecol Evol. 2017 Jul 3;1(8):1192–1200. doi: 10.1038/s41559-017-0226-3 図の説明： d, Expression of sox2 and k81 in control embryos and in embryos injected with zBMP4, nodal or both recombinant proteins. Scale bar, 250 μm. 方法： Xenopus embryos were injected in the blastocoel with 10 ng mouse recombinant Nodal protein (R&D), 3.5 ng zebrafish recombinant BMP4 protein (R&D), or 30 ng recombinant human Noggin (R&D).
Fig. 4. Temporal and spatial expression of Xnr-1 and Xnr-2 during Xenopus development.(B-H) Whole-mount in situ hybridization analysis of Xnr-1 and Xnr-2 expression. All embryos are cleared albino embryos, viewed from the vegetal surface with dorsal oriented upward. The dorsal lip is indicated by the black arrowhead. (B) Stage 9 embryos show punctate perinuclear Xnr-1 signal over the entire vegetal region. Xnr-2 shows the same pattern (data not shown). (C) Xnr-1 signal at stage 10.25 is restricted to the dorsal marginal zone (dark arc at bottom left is a background artefact). (D) Xnr-2 signal in stage 10 pregastrula is primarily located in the dorsal marginal zone, but also in adjacent dorsovegetal cells. (E) Xnr-2 signal in the stage 10.5 gastrula is highly concentrated just above the dorsal lip, with a gradual decrease laterally and ventrally. (F) Whole-mount stained stage 10.25 embryo, split open along the dorsal/ventral plane and viewed internally to show Xnr-2 expression at the dorsal lip. Superficial and slightly deeper staining is observed. Some out-of-focus vegetal cells below the lip express Xnr-2 (white arrowhead). https://journals.biologists.com/dev/article/121/11/3651/38534/Nodal-related-signals-induce-axial-mesoderm-and
Several TGFβ ligands present in the blastula embryo, including Activin, Vg1, Derriere and the Nodal-related factors Xnr1 and Xnr2, each have the ability to induce the expression of both general and organizer-specific mesodermal markers (Asashima et al., 1990; Smith et al., 1990; Thomsen et al., 1990; Thomsen and Melton, 1993; Jones et al., 1995; Kessler and Melton, 1995; Sun et al., 1999).
Genetic studies in the mouse and zebrafish demonstrate a requirement for Nodal-related genes in mesoderm and organizer formation (Schier and Shen, 2000).
Loss-of-function mutations in the mouse and the zebrafish Nodal genes result in embryos which fail to form an organizer and lack mesoderm (Conlon et al., 1994; Feldman et al., 1998). Likewise, inhibition of Nodal signaling in Xenopus, using a Nodal-specific form of Cerberus, blocks mesoderm and organizer formation (Agius et al., 2000).
While Nodal signaling induces mesoderm in the equatorial region of the blastula, the organizer forms in a dorsal equatorial domain in response to maternal Wnt signaling (reviewed in Harland and Gerhart, 1997; Heasman, 1997; Moon and Kimelman, 1998).
Wnt3 and Nodal function are required in the mouse for gastrulation and node formation (Liu et al., 1999; Conlon et al., 1994),
Cooperation of Siamois and TGFβ signals Siamois cooperates with TGFβ signals to induce the complete function of the Spemann-Mangold Organizer MARK J. ENGLEKA and DANIEL S. KESSLE Int. J. Dev. Biol. 45: 241-250 (2001) 241
Fig. 2. The spatial distribution of Xnr5 and Xnr6 expression was analyzed by whole-mount in situ hybridization as previously described (Harland, 1991). The spatial distribution of Xnr5 and Xnr6 expression was analyzed by whole-mount in situ hybridization as previously described (Harland, 1991). In the late blastula embryo, Xnr5 and Xnr6 mRNA was detected from the vegetal pole to the dorsal vegetal region, including the Nieuwkoop center (Fig. 2D-F). At early gastrula, an Xnr6 signal was seen at just beneath the dorsal lip (Fig. 2G), whereas no Xnr5 signal could be detected at this stage (data not shown). Unlike Xnr3 (Fig. 2B,C), Xnr5 and Xnr6 transcripts did not localize at the Spemann’s organizer.
Secondary axis induction by Xnr5 and Xnr6. https://journals.biologists.com/dev/article/127/24/5319/41043/Two-novel-nodal-related-genes-initiate-early
These results indicate that the structures of Xnr5 and Xnr6 are quite similar to Xnr1 and Xnr2. All of these four factors can induce a secondary axis lacking the head structures when they are misexpressed ventrally. Xnr4 also has similar activity (S. T., C. Y., Y. O. and M. A., unpublished).
Cerberus is a head-inducing secreted factor (Bouwmeester et al., 1996) that acts as a multifunctional antagonist of Nodal, BMP (Bone Morphogenetic Proteins) and Wnt signals (Hsu et al., 1998; Piccolo et al., 1999). A carboxy-terminal fragment of Cerberus, called Cerberus-short (Cer-S), lacks the anti-Wnt and anti-BMP activities but retains full anti-Xnr1 activity (Piccolo et al., 1999). In biochemical studies, Cer-S was found to bind Xnr1, but not Activin nor Vg1 proteins (Piccolo et al., 1999). https://pmc.ncbi.nlm.nih.gov/articles/PMC2292107/
Endodermal Nodal-related signals and mesoderm induction in Xenopus Eric Agius 1,*,‡, Michael Oelgeschläger 1,*, Oliver Wessely 1, Caroline Kemp 1, E M De Robertis 1,§ Development. 2000 Mar;127(6):1173–1183. doi: 10.1242/dev.127.6.1173
Smad2 mediates Activin/Nodal signaling in mesendoderm differentiation of mouse embryonic stem cells Teng Fei, Shanshan Zhu, Kai Xia, Jianping Zhang, Zhongwei Li, Jing-Dong J Han & Ye-Guang Chen Cell Research volume 20, pages1306–1318 (2010) https://www.nature.com/articles/cr2010158
FELDMAN, B., GATES, M.A., EGAN, E.S., DOUGAN, S.T., RENNEBECK, G., SIROTKIN, H.I., SCHIER, A.F. and TALBOT, W.S. (1998). Zebrafish organizer development and germ-layer formation require nodal-related signals. Nature 395: 181-185.
Neural induction and early patterning in vertebrates Mohammad Zeeshan Ozair 1, Chris Kintner 2, Ali H Brivanlou 1,* Wiley Interdiscip Rev Dev Biol. 2012 Oct 15;2(4):479–498. doi: 10.1002/wdev.90 https://pmc.ncbi.nlm.nih.gov/articles/PMC6945772/
Dimeric TGFβ ligands bind type II receptors that phosphorylate and activate type I receptors in a hetero-tetrameric complex. Receptor activation, in turn, leads to the propagation of signaling by at least two pathways involving Smad (in the canonical pathway) or Traf/TGFβ-Activated-Kinase-1 (TAK1, in the non-canonical pathway).
Neural induction and early patterning in vertebrates Mohammad Zeeshan Ozair, Chris Kintner, Ali H Brivanlou Wiley Interdiscip Rev Dev Biol. 2012 Oct 15;2(4):479–498. doi: 10.1002/wdev.90 https://pmc.ncbi.nlm.nih.gov/articles/PMC6945772/
Synergism between temporally distinct growth factors: bFGF, insulin and lens cell differentiation Author links open overlay panel W.P.J. Leenders , S.T. van Genesen , J.G.G. Schoenmakers 1 , E.J.J. van Zoelen , N.H. Lubsen Mechanisms of Development Volume 67, Issue 2, October 1997, Pages 193-201 Mechanisms of Development https://www.sciencedirect.com/science/article/pii/S0925477397001214
神経誘導
Involvement of BMP-4/msx-1 and FGF pathways in neural induction in the Xenopus embryo DGD 25 December 2001 https://onlinelibrary.wiley.com/doi/full/10.1046/j.1440-169x.2000.00514.x
