The term ‘organization centre’ was first introduced by Hans Spemann (Spemann and Mangold, 1924)
the blastopore lip of the early gastrula of the newt Triturus taeniatus had the ability to cause the formation of a full axis when transplanted onto the opposite side of a similarly staged embryo of Triturus cristatus, a different unpigmented species.
the 1924 report could discern between the host and the graft by pigment differences, which revealed the important point that the ectopic tissue developed from the host tissue.
On the nature and function of organizers Alfonso Martinez Arias* and Ben Steventon* Development. 2018 Mar 1; 145(5): dev159525. PMCID: PMC5868996
Hilde Mangold: Original microscope slides and records of the gastrula organizer experiments Wolfgang Driever a b, Jochen Holzschuh a, Luise Sommer c, Roland Nitschke b d, Angela Naumann b d, Jenny Elmer c 1, Peter Giere c Cells & Development 28 February 2024, 203909
他の動物種でも同様の実験が行われて同様の結果が得られたことから、「誘導」という概念が確立しました。
the organizer is responsible for neural induction
the organizer dorsalizes the mesoderm
Induction into the Hall of Fame: tracing the lineage of Spemann’s organizer Richard Harland Author and article information 15 OCTOBER 2008 Development (2008) 135 (20): 3321–3323.
Spemann-Mangold organizer and mesoderm induction Makoto Asashima, Yumeko Satou-Kobayashi Cells & Development Available online 1 February 2024, 203903
上の図では中胚葉が外胚葉に働きかけて神経誘導を行うことが模式的に示されています。
Introducing the Spemann-Mangold organizer: experiments and insights that generated a key concept in developmental biology Int. J. Dev. Biol. 45: 1-11 (2001) PDF
Spemann and Mangold (Spemann and Mangold, 1924) provided the initial insight showing that transplantation of dorsal lip mesoderm of the gastrulating amphibian embryo would induce an ectopic secondary axis that included a central nervous system (CNS). This led to the view that neural inducers emanate from dorsal mesoderm, a region also called Spemann’s organizer.
neural induction may start very early in development with signals mediated by the β-Catenin pathway.
Neural Induction in the Absence of Mesoderm: β-Catenin Dependent Expression of Secreted BMP Antagonists at the Blastula Stage in Xenopus Oliver Wessely,1 Eric Agius,1,2 Michael Oelgeschläger, Edgar M. Pera, and E. M. De Robertis* Dev Biol. 2001 Jun 1; 234(1): 161–173. doi: 10.1006/dbio.2001.0258 PMCID: PMC3039525 NIHMSID: NIHMS43280 PMID: 11356027
Head organizer: Cerberus and IGF cooperate in brain induction in Xenopus embryos agmur Azbazdar a, Edgar M. Pera b, Edward M. De Robertis a Cells & Development Available online 16 December 2023, 203897 Spemann later found that early dorsal blastopore lips induced heads and late organizers trunk-tail structures. Identifying region-specific organizer signals has been a driving force in the progress of animal biology. Head induction in the absence of trunk is designated archencephalic differentiation. Two specific head inducers, Cerberus and Insulin-like growth factors (IGFs), that induce archencephalic brain but not trunk-tail structures have been described previously.
Neural and Head Induction by Insulin-like Growth Factor Signals Edgar M. Pera, Oliver Wessely, Su-Yu Li, E.M. De Robertis Developmental Cell Volume 1, Issue 5, November 2001, Pages 655-665
FGF activity induces both ERNI [18,36] and Geminin (this study) in the epiblast.
Geminin binds to the chromoshadow-binding domain of Brm, displacing HP1α (Figure 4G).
the interaction of ERNI with Geminin recruits the transcriptional repressor HP1γ, thus continuing to prevent premature expression of Sox2 in the epiblast (Figure 7E).
ＦGF is required for both mesodermal [51–54] and neural induction [36,55,56]. 同じシグナルを受けて異なる分化をとげるメカニズムは、受けて側のタイミングや場所の違いによると考えられる
BERT is up-regulated within the neural plate, where it binds to both ERNI and Geminin and displaces ERNI-HP1γ complexes away from Brm, freeing the latter to activate N2 and thus Sox2 expression (Figure 9M).
We propose that BERT disrupts the interaction between Geminin and ERNI, displacing HP1γ from the N2 enhancer and thus allowing Geminin/Brahma(Brm) to induce Sox2 expression.（Ｆｉｇ．９Ｍ）
FGF signaling activates ERNI as well as Sox3 and Geminin expression in the epiblast.
A Mechanism Regulating the Onset of Sox2 Expression in the Embryonic Neural Plate 2008年 https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0060002
Molecular Biology of the CellVol. 18, No. 6ArticlesFree Access The Activity of Pax3 and Zic1 Regulates Three Distinct Cell Fates at the Neural Plate Border This is the final version – click for previous version Chang-Soo Hong, and Jean-Pierre Saint-Jeannet Marianne Bronner-Fraser, Monitoring Editor Published Online:4 Apr 2007 https://doi.org/10.1091/mbc.e06-11-1047
分子シグナリング
the neural inducers, Noggin, Chordin, and Follistatin emanate from Spemann’s organizer.3,4,5
Noggin, Chordin, and Follistatin directly bind to bone morphogenetic proteins, namely, BMP2/4/7, in the extracellular space and act as antagonists to block these BMPs from binding to the BMP receptor.6
the blockade of BMP signaling inhibits the phosphorylation of the carboxyl-terminal serine residues of the Smad1 protein, which is an intracellular mediator of the BMP signal, preventing the downstream genes of BMP signals from being activated.
the inhibition of the BMP signal induces the expression of a series of transcription factors, which in turn activate the downstream transcriptional network to further promote neural differentiation.
FGF promotes the phosphorylation of the intermediate linker domain of the Smad1 protein, instead of its carboxyl-terminal domain, and restricts the Smad1 activity.7
the combination of BMP inhibitors and FGF is essential for directing naive cells toward the neural fate.
In mouse embryos, Chordin and Noggin homologues emanate from the node, or the anterior portion of the primitive streak, and t
Chordin/Noggin double mutants exhibit severe forebrain malformation at early embryonic stages,11,12 but the development of the posterior nervous system in the Chordin/Noggin double mutant mice is relatively normal （両生類のように神経誘導すべてが抑制されるのとは事情が異なる。
哺乳類では、the anterior and posterior neural cells are already separated at the epiblast stage, and this differentiation progresses independently.13,14
The Organizer and Its Signaling in Embryonic Development Vijay Kumar,1 Soochul Park,2 Unjoo Lee,3,* and Jaebong Kim1, J Dev Biol. 2021 Dec; 9(4): 47. Published online 2021 Nov 1. PMCID: PMC8628936
Cell communication with the neural plate is required for induction of neural markersby BMP inhibition: evidence for homeogenetic induction and implications forXenopus animal cap and chick explant assays Claudia Linkera,⁎,1, Irene De Almeidaa, Costis Papanayotoua, Matthew Stowera, Virginie Sabadob,Ehsan Ghorania, Andrea Streitb, Roberto Mayora, Claudio D. Stern Developmental Biology 327 (2009) 478–486 ResearchGate
BMＰとTGF-beta signaling
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) superfamily. BMPs were originally identified from bone matrix using an ectopic bone formation assay.
About 60 TGF-β family members have been identified so far7 with two general branches: (i) BMP/growth and differentiation factor (GDF) and (ii) the TGF-β/activin/nodal branch/mullerian-inhibiting substance or anti-mullerian hormone.8
TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation Rahman et al., Bone Res. 2015; 3: 15005. PMCID: PMC4472151
The dorsalizing and neural inducing gene follistatin is an antagonist of BMP-4 Fainsod et al., Mechanisms of Development Volume 63, Issue 1, April 1997, Pages 39-50 Mechanisms of Development https://www.sciencedirect.com/science/article/pii/S0925477397006734
The transforming growth factor-beta (TGF-β) family of cytokines, including TGF-β, bone morphogenic proteins (BMPs), and activin/inhibin, plays crucial roles in embryonic development, adult tissue homeostasis and the pathogenesis of a variety of diseases.
The highly conserved core of the canonical TGF-β/BMP signaling is a simple linear cascade that involves the TGF-β/BMP ligands, two types of receptors (type I and II) and the signal transducers, Smads.
On activation, the receptor complex phosphorylates the carboxy-terminus of receptor-regulated Smad proteins (R-Smads), including Smad1, 5 and 8 for BMP signaling and Smad2 and 3 for TGF-β signaling.
Activated R-Smads interact with the common partner Smad, Smad4, and accumulate in the nucleus, where the Smad complex directly binds defined elements on the DNA and regulates target gene expression together with numerous other factors [1–3].
Signaling cross-talk between TGF-β/BMP and other pathways Guo and Wang Cell Res. 2009 Jan; 19(1): 71–88. PMC3606489
We have identified a new member of the transforming growth factor-beta (TGF-beta) superfamily, growth/differentiation factor-10 (GDF-10), which is highly related to bone morphogenetic protein-3 (BMP-3).
Growth/differentiation factor-10: a new member of the transforming growth factor-beta superfamily related to bone morphogenetic protein-3 N S Cunningham 1, N A Jenkins, D J Gilbert, N G Copeland, A H Reddi, S J Lee Growth Factors . 1995;12(2):99-109. doi: 10.3109/08977199509028956. https://pubmed.ncbi.nlm.nih.gov/8679252/
Bone morphogenetic protein signaling: the pathway and its regulation Takuya Akiyama, Laurel A Raftery, Kristi A Wharton Author Notes Genetics, Volume 226, Issue 2, February 2024, iyad200, https://doi.org/10.1093/genetics/iyad200
BMP signaling during craniofacial development: new insights into pathological mechanisms leading to craniofacial anomalies Hiroki Ueharu and Yuji Mishina Front Physiol. 2023; 14: 1170511. 2023 May 18.
