In embryology, the term “definitive” is used to describe structures or stages that are mature, final, or fully developed. This contrasts with earlier, transient, or intermediate forms that occur during development. Here are some examples of how “definitive” is used in this context:
Definitive Yolk Sac: The final form of the yolk sac, as opposed to the primitive yolk sac that appears earlier in development.
Definitive Blood Circulation: The mature circulatory system that is established after the temporary, embryonic circulatory systems have been replaced.
Definitive Structures: Refers to the adult forms of tissues, organs, or body parts that have completed their development.
In summary, “definitive” in embryology signifies the end stage of a developmental process, when the structure has reached its final, functional form.
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Notochordal Process: This is an early, tubular structure formed from the axial mesoderm. It represents a precursor to the fully formed notochord.
Notochordal Plate: As the notochordal process develops, it transforms into a flattened structure called the notochordal plate, which then folds to form the definitive notochord.
Iimura and Pourquié 2006Nature . 2006 Aug 3;442(7102):568-71. doi: 10.1038/nature04838. Epub 2006 Jun 7. Collinear activation of Hoxb genes during gastrulation is linked to mesoderm cell ingression Tadahiro Iimura, Olivier Pourquié PDF (ResearchGate)
上記論文以外にどれがエビデンスとなりえるのか、ちょっとわかりずらいです。
Vertebrate hox temporal collinearity: does it exist and what is it’s function? A. J. Durston Pages 523-530 | Received 05 Dec 2018, Accepted 09 Jan 2019, Published online: 15 Feb 2019 https://www.tandfonline.com/doi/full/10.1080/15384101.2019.1577652
Some Questions and Answers About the Role of Hox Temporal Collinearity in Vertebrate Axial PatterningAntony J. Durston* PERSPECTIVE article Front. Cell Dev. Biol., 29 November 2019 Sec. Evolutionary Developmental Biology Volume 7 – 2019 | https://doi.org/10.3389/fcell.2019.00257 Does Hox Temporal Collinearity Exist?
comprehensive analysis of hox gene expression during early development did not agree with the hypothesis of temporal collinearityespecially in genes belonging to PG2 to PG10.
though the complete set of hox genes are identified in many animals, no comprehensive analysis of temporal expression during development has been reported.
This is the first comprehensive analysis of hox gene expression during development in vertebrates, and the data questions the hypothesis of temporal collinearity.
the “temporal collinearity hypothesis” must be revisited by comprehensive analysis for developmental timing of transcriptional initiation of hox genes, because this hypothesis implicitly includes the idea that de novo mRNA synthesis of hox genes occurs from anterior to posterior paralogous groups, even though no experiment examining de novo mRNA synthesis of hox genes has been ever reported.
Comprehensive analyses of hox gene expression in Xenopus laevis embryos and adult tissues Mariko Kondo 1, Takayoshi Yamamoto 2, Shuji Takahashi 3, Masanori Taira 2 Dev Growth Differ . 2017 Aug;59(6):526-539. doi: 10.1111/dgd.12382. Epub 2017 Aug 9.
Some Questions and Answers About the Role of Hox Temporal Collinearity in Vertebrate Axial PatterningAntony J. Durston* PERSPECTIVE article Front. Cell Dev. Biol., 29 November 2019 Sec. Evolutionary Developmental Biology Volume 7 – 2019 | https://doi.org/10.3389/fcell.2019.00257
結局、原著論文を自分で読んで判断するしかなさそうですね。よくみたら自分が見つけたtemporal collinearity仮説を支持するレビュー論文3報は3報とも同じ著者Antony J. Durstonさんでした。
In these earliest developmental stages, morphogen concentration gradients are not relevant for setting up this axis. It emerges that at these stages, the core patterning mechanism is timing: BMP-anti BMP mediated time space translation that regulates Hox temporal and spatial collinearities and Hox-Hox auto- and cross- regulation. The known anterior-posterior morphogens and signaling pathways–retinoids, FGF’s, Cdx, Wnts, Gdf11 and others–interact with this core mechanism at and after space-time defined “decision points,” leading to the separation of distinct axial domains.
What are the roles of retinoids, other morphogens, and Hox genes in setting up the vertebrate body axis? Genesis . 2019 Jul;57(7-8):e23296. doi: 10.1002/dvg.23296. Epub 2019 Apr 25. Antony J Durston https://pubmed.ncbi.nlm.nih.gov/31021058/
LIFE UNFOLDINGをよむと、一つのクラスタ内の複数のHOX遺伝子を端から順にほどいて読んでいく時間差と細胞移動によって生じる空間の違いとが連動していると紹介されていました。DNAはヌクレオソーム（ヒストン蛋白質８量体にDNAがまきついた複合体）構造をとりますが、一つのヌクレオソームを構成するDNAの長さは146bpで、複数のヌクレオソームがさらに折り畳まれて存在しています。HOXクラスタの長さは140kbくらいだそうです。
In chordates, Hox genes are classified into 13 paralog groups (PGs) according to homeodomain similarity [2]. Hox genes are often found in a relatively narrow region on one chromosome, forming a Hox gene cluster. It is generally accepted that the Hox gene cluster consists of a subset of the 13 PG Hox genes, which are aligned according to PG number, and that have the same transcription direction, spanning about 100–120 kb on a chromosome. https://zoologicalletters.biomedcentral.com/articles/10.1186/s40851-017-0078-3
核内で転写が起きる場所
転写は核内でどこででも起きるわけではなく、転写が起きる場所というものが定まってるようです。
There is considerable evidence that transcription does not occur homogeneously or diffusely throughout the nucleus, but rather at a number of specialized, discrete sites termed transcription factories. https://www.researchgate.net/profile/Dietmar-Rieder/publication/232739705_Transcription_factories/links/09e4151094770d5dda000000/Transcription-factories.pdf
レチノイン酸がHOX遺伝子の発現を誘導する実験的な証拠
The expression of murine Hox-2 genes is dependent on the differentiation pathway and displays a collinear sensitivity to retinoic acid in F9 cells and Xenopus embryos N Papalopulu, R Lovell-Badge, R Krumlauf Nucleic Acids Res . 1991 Oct 25;19(20):5497-506. doi: 10.1093/nar/19.20.5497. https://pubmed.ncbi.nlm.nih.gov/1682879/
Human HOX genes are differentially activated by retinoic acid in embryonal carcinoma cells according to their position within the four loci Cell Differentiation and Development Volume 31, Issue 2, August 1990, Pages 119-127 https://www.sciencedirect.com/science/article/pii/092233719090015O NT2/D1細胞でレチノイン酸添加によるヒトHOX遺伝子33個の発現への効果を調べた。
レチノイン酸とFGFとHOX遺伝子
Opposing FGF and retinoid pathways: a signalling switch that controls differentiation and patterning onset in the extending vertebrate body axis Ruth Diez del Corral 1, Kate G Storey Affiliations expand PMID: 15273988 DOI: 10.1002/bies.20080 Bioessays . 2004 Aug;26(8):857-69. doi: 10.1002/bies.20080.
The individual Hox genes are expressed in strict temporal sequence determined by their position in the Hox gene cluster(temporal colinearity), the more 3′ genes first and subsequently the more 5′. https://journals.biologists.com/dev/article/130/20/4823/52226/Enhancer-timing-of-Hox-gene-expression-deletion-of
What is the connection between axial identity, Hox genes, and the system of graded RA, Wnt, and FGF signaling? It is important to first distinguish between the initiation of Hox gene expression during gastrulation and the subsequent repositioning of expression boundaries within the PSM and somites (Deschamps and van Nes 2005). During the initiation phase, Hox genes become activated in a striking temporal collinearity within the primitive streak region. This precise sequential activation serves a critical function in contributing to the final spatial collinearity along the body axis (Forlani et al. 2003; Juan and Ruddle 2003; Wacker et al. 2004; Iimura and Pourquié 2006), which ultimately determines axial identity. Importantly, however, this initial blueprint does not entirely match the definitive Hox gene expression (Forlani et al. 2003). Thus, the definitive Hox gene identity does not strictly result from the collinear initiation phase alone, but also from extensive modification of Hox gene expression occurring after cells exit the primitive streak and before they are incorporated into a somite (i.e., while located in the PSM).
Iimura and Pourquié 2006Nature . 2006 Aug 3;442(7102):568-71. doi: 10.1038/nature04838. Epub 2006 Jun 7. Collinear activation of Hoxb genes during gastrulation is linked to mesoderm cell ingression Tadahiro Iimura, Olivier Pourquié PDF (ResearchGate)
Initiation, establishment and maintenance of Hox gene expression patterns in the mouse February 1999The International Journal of Developmental Biology 43(7):635-50 February 199943(7):635-50
Two phases in the establishment of HOX expression domains J Deschamps 1, M Wijgerde Affiliations expand PMID: 8096483 DOI: 10.1006/dbio.1993.1093 Dev Biol . 1993 Apr;156(2):473-80. doi: 10.1006/dbio.1993.1093.
HOXコードによる位置決め
Hox9 genes and vertebrate limb specification M J Cohn 1, K Patel, R Krumlauf, D G Wilkinson, J D Clarke, C Tickle Nature. 1997 May 1;387(6628):97-101. doi: 10.1038/387097a0.
Spatially Restricted Domains of Homeo-Gene Transcripts in Mouse Embryos – Relation to a Segmented Body Plan October 1988 Development 104(Supplement) October 1988104(Supplement) DOI:10.1242/dev.104.Supplement.169 体軸に沿って発現する位置がHOX遺伝子では異なっていることを示した初期の論文
https://www.researchgate.net/profile/Dietmar-Rieder/publication/232739705_Transcription_factories/links/09e4151094770d5dda000000/Transcription-factories.pdf