In mice, around embryonic day (E) 6.0, at the time when gastrulation begins, mouse PGCs (mPGCs) are specified as about 10 cells in the most posterior part of epiblast, the cup-shaped simple pluripotent epithelium, from which all of the embryonic portion are derived (Fig. 1.1). This process occurs in response to bone morphogenetic protein 4 (BMP4) [25] produced by the extraembryonic ectoderm (ExE), an extraembryonic part of conceptus in intimate contact with the edge of the epiblast (Fig. 1.1). https://www.sciencedirect.com/topics/engineering/extraembryonic-ectoderm
Migrating mesoderm cells self-organize into a dynamic meshwork structure during chick gastrulation Yukiko Nakaya, Mitsusuke Tarama, Sohei Tasaki, Ayako Isomura, View ORCID ProfileTatsuo Shibata doi: https://doi.org/10.1101/2022.09.08.507227 Posted September 09, 2022. https://www.biorxiv.org/content/10.1101/2022.09.08.507227v1.full
Cell movement during chick primitive streak formation Developmental Biology Volume 296, Issue 1, 1 August 2006, Pages 137-149 細胞の動きを示したsupplementary movie 動画がいくつかあります https://www.sciencedirect.com/science/article/pii/S0012160606007299
Cell Movement Patterns during Gastrulation in the Chick Are Controlled by Positive and Negative Chemotaxis Mediated by FGF4 and FGF8 Developmental Cell Volume 3, Issue 3, September 2002, Pages 425-437 https://www.sciencedirect.com/science/article/pii/S1534580702002563 細胞移動の軌跡を示した動画がいくつかあります。FGF8とFGF4の役割についても非常にわかりやすい実験結果
Self-Organizing Properties of Mouse Pluripotent Cells Initiate Morphogenesis upon Implantation Cell Volume 156, Issue 5p1032-1044February 27, 2014 https://www.cell.com/fulltext/S0092-8674%2814%2900075-0
AEV特異的マーカータンパク質の早期の時期における発現
AVE protein expression and visceral endoderm cell behavior during anterior-posterior axis formation in mouse embryos: Asymmetry in OTX2 and DKK1 expression. Developmental biology Hideharu Hoshino et al. 36 citations 2015 https://www.sciencedirect.com/science/article/pii/S0012160615001748 AVEマーカータンパク質のステージE4.5の時期の発現
Nodal signaling from the visceral endoderm is required to maintain Nodal gene expression in the epiblast and drive DVE/AVE migration Developmental Biology Volume 400, Issue 1, 1 April 2015, Pages 1-9 Developmental Biology https://pdf.sciencedirectassets.com/272543/1-s2.0-S0012160615X00054/1-s2.0-S0012160614006460/main.pdf
Hex: a homeobox gene revealing peri-implantation asymmetry in the mouse embryo and an early transient marker of endothelial cell precursors Development . 1998 Jan;125(1):85-94. doi: 10.1242/dev.125.1.85. https://journals.biologists.com/dev/article/125/1/85/39778/Hex-a-homeobox-gene-revealing-peri-implantation
From fertilization to gastrulation: axis formation in the mouse embryo. Curr Opin Genet Dev . 2001 Aug;11(4):384-92. DOI:10.1016/S0959-437X(00)00208-2Corpus ID: 17925624
Vertebrate Axial Patterning: From Egg to Asymmetry. Advances in Experimental Medicine and Biology, 01 Jan 2017, 953:209-306 https://doi.org/10.1007/978-3-319-46095-6_6 PMID: 27975274 PMCID: PMC6550305 https://europepmc.org/article/pmc/pmc6550305
DVEがAVEの位置に移動するためにはnodalシグナルが必要なようです。
Nodal signaling from the visceral endoderm is required to maintain Nodal gene expression in the epiblast and drive DVE/AVE migration Developmental Biology Volume 400, Issue 1, 1 April 2015, Pages 1-9 Developmental Biology https://pdf.sciencedirectassets.com/272543/1-s2.0-S0012160615X00054/1-s2.0-S0012160614006460/main.pdf
AVEで発現する遺伝子
AVE protein expression and visceral endoderm cell behavior during anterior-posterior axis formation in mouse embryos: Asymmetry in OTX2 and DKK1 expression. Developmental biology Hideharu Hoshino et al. 36 citations 2015 https://www.sciencedirect.com/science/article/pii/S0012160615001748 ステージE6.5でのAVEにおける特異的なタンパク質の発現
Axis Development and Early Asymmetry in Mammals Cell Volume 96, Issue 2p195-209 January 22, 1999 https://www.cell.com/fulltext/S0092-8674%2800%2980560-7
At the blastocyst stage, the polar TE lies adjacent to the epiblast and is fated to form the extraembryonic ectoderm and ectoplacental cone, which will subsequently form the fetal portion of the placenta, whereas the mural TE initially encloses the blastocyst cavity and eventually forms the outer layer of the parietal yolk sac.
Between E5.5 and E6.0, the proamniotic cavity expands to the extraembryonic ectoderm, forming the proamniotic canal.
Axis Development and Early Asymmetry in Mammals Cell Volume 96, Issue 2p195-209January 22, 1999 https://www.cell.com/fulltext/S0092-8674%2800%2980560-7
The role of BMP4 signaling in trophoblast emergence from pluripotencyCellular and Molecular Life Sciences 25 July 2022 Volume 79, article number 447, (2022)
Fig.1 Whole-mount in situ hybridisation analysis showing asymmetrical Hex expression in the visceral endoderm of pregastrulation stage embryos. (A-C) 4.5 dpc blastocysts showing Oct-4 expression (A) in the inner cell mass and Hex expression (B,C) in the primitive endoderm (black arrowhead). (D,E) Hex expression (black arrowhead) in the distal tip visceral endoderm of 5.5 dpc embryos. Note that the Hex expression domain is immediately proximal to the distal tip in the slightly older embryo shown in E. (F,G) Double in situ hybridisation analysis ofHex (black arrowhead) and T (white arrowhead) at 6.0 dpc (F) and 6.5 dpc (G). Hex expression at 6.0 dpc is clearly asymmetrical within the endoderm prior to the accumulation of T transcripts to the nascent primitive streak at the posterior pole of the embryo (G). Bar, 40 μm (A-C); 50 μm (D); 60 μm (E-G).
Hex: a homeobox gene revealing peri-implantation asymmetry in the mouse embryo and an early transient marker of endothelial cell precursors Development (1998) 125 (1): 85–94. 01 January 1998
In humans, a structure equivalent to the mouse extraembryonic ectoderm is not thought to form.
Pluripotent Stem Cells Susana M. Chuva de Sousa Lopes, Christine L. Mummery, in Handbook of Stem Cells (Second Edition) , 2013 https://www.sciencedirect.com/topics/engineering/extraembryonic-ectoderm
In the post-implantation mouse embryo, formation of the PS and initiation of germ layer formation are driven by signaling activities emanating from the extraembryonic tissues such as the extraembryonic ectoderm, which gives rise to chorionic ectoderm, and visceral endoderm and from within the epiblast. However, in primates, there is no clear equivalent to the TE-derived extraembryonic ectoderm of the mouse, which is a major source of BMP to induce gastrulation and primitive-streak formation. In humans and nonhuman primates, the amnion (amniotic epithelium) is reputed to behave like a signaling center of BMP activity to induce the differentiation of mesoderm in the Cynomolgus embryonic disc and the human PASE (Shao et al., 2017; Yang et al., 2021; Zheng et al., 2019). https://www.cell.com/developmental-cell/pdf/S1534-5807(21)01042-X.pdf
そうなるとヒトの場合は、どこから最初のシグナルが来るの？という疑問が湧きます。
Early mouse embryonic development. As described in the text, the blastocyst at 3.5 dpc consists of two tissues: the inner cell mass and trophectoderm. At 4.5 dpc the primitive endoderm is formed and the embryo starts to implant into the uterine wall. By 5.5 dpc, the embryo is cup-shaped https://www.researchgate.net/figure/Early-mouse-embryonic-development-As-described-in-the-text-the-blastocyst-at-35-dpc_fig1_228357767
BMP4シグナル
Front Cell Dev Biol. 2024 Apr 22;12:1386739. doi: 10.3389/fcell.2024.1386739 A comprehensive review: synergizing stem cell and embryonic development knowledge in mouse and human integrated stem cell-based embryo models https://pmc.ncbi.nlm.nih.gov/articles/PMC11074781/
上皮ー間葉転換 EMT
Basal delamination during mouse gastrulation primes pluripotent cells for differentiation https://pmc.ncbi.nlm.nih.gov/articles/PMC7616279/
Distinct predictive performance of Rac1 and Cdc42 in cell migration ScienceVio チャンネル登録者数 8620人 Published: 04 December 2015 Distinct predictive performance of Rac1 and Cdc42 in cell migration Masataka Yamao, Honda Naoki, Katsuyuki Kunida, Kazuhiro Aoki, Michiyuki Matsuda & Shin Ishii Scientific Reports volume 5, Article number: 17527 (2015)
ニワトリ胚の中胚葉細胞の移動経路
Cell movement patterns during gastrulation in the chick are controlled by positive and negative chemotaxis mediated by FGF4 and FGF8 Dev Cell . 2002 Sep;3(3):425-37. doi: 10.1016/s1534-5807(02)00256-3. https://www.cell.com/developmental-cell/fulltext/S1534-5807(02)00256-3 蛍光標識した 原始結節(node)の移植片の細胞の移動経路を経時的に観察
Fates and migratory routes of primitive streak cells in the chick embryo Delphine Psychoyos, Claudio D. Stern Author and article information Development (1996) 122 (5): 1523–1534. 01 May 1996 https://journals.biologists.com/dev/article/122/5/1523/39034/Fates-and-migratory-routes-of-primitive-streak
ニワトリ胚のFGFの役割
FGF signalling through RAS/MAPK and PI3K pathways regulates cell movement and gene expression in the chicken primitive streak without affecting E-cadherin expression Katharine M Hardy, Tatiana A Yatskievych, JH Konieczka, Alexander S Bobbs & Parker B Antin BMC Developmental Biology volume 11, Article number: 20 (2011) Published: 21 March 2011 https://bmcdevbiol.biomedcentral.com/articles/10.1186/1471-213X-11-20
Gene expression pattern Expression of Fgf4 during early development of the chick embryo Mechanisms of Development Volume 85, Issues 1–2, 1 July 1999, Pages 189-192 https://www.sciencedirect.com/science/article/pii/S0925477399000933
FGF Signaling Regulates Mesoderm Cell Fate Specification and Morphogenetic Movement at the Primitive Streak Developmental Cell Volume 1, Issue 1p37-49July 2001 https://www.cell.com/developmental-cell/fulltext/S1534-5807(01)00017-X
マウス胚のFGFの役割
Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo Genes & Dev. 1999. 13: 1834-1846 https://genesdev.cshlp.org/content/13/14/1834/F1.expansion.html
AK Hadjantonakis: Cell lineage specification & tissue morphogenesis in the early mouse embryo. Genetics Society of America チャンネル登録者数 2040人
CerberusやDickkopfによるWntシグナリングの阻害
Heads or tails: Wnts and anterior–posterior patterning Terry P Yamaguchi Current Biology Volume 11, Issue 17pR713-R724 September 04, 2001 https://www.cell.com/current-biology/fulltext/S0960-9822%2801%2900417-1
nordal
The ability of the Nodal pathway to induce both mesoderm specification and axis extension in explants is consistent with its role in vivo, where Nodal is necessary for both (37–40). For example, mouse embryos mutant for Nodal signaling components fail to gastrulate entirely (41). Zebrafish embryos lacking all Nodal function – through loss of the coreceptor Tdgf1/Cripto (MZoep-/-) (40), ligands (sqt-/-cyc-/-) (38), or downstream effector Smad2 (MZsmad2-/-) (42) – similarly lack all endoderm and most mesoderm and undergo abnormal gastrulation movements resulting in a severely shortened AP axis.
Temporal dynamics of BMP/Nodal ratio drive tissue-specific gastrulation morphogenesis https://www.biorxiv.org/content/10.1101/2024.02.06.579243v1.full
Eomes, Criptなどのシグナル分子
From fertilization to gastrulation: axis formation in the mouse embryo. Curr Opin Genet Dev . 2001 Aug;11(4):384-92. DOI:10.1016/S0959-437X(00)00208-2Corpus ID: 17925624
a–l, Whole-mount in situ hybridization analysis. a, Uniform symmetric staining in the epiblast at 5.5 d.p.c.; b, a cross section shows lack of expression in the visceral endoderm. c, d, Proximal–distal gradient of expression in the epiblast. e, Sagittal section of d. f, g, Expression shifts caudally before the onset of gastrulation at 6.5 d.p.c. h, Cross-section of g shows widespread expression in the epiblast and no expression in the visceral endoderm. i, Mid-streak stage; j, cross-section shows intense staining in the newly formed embryonic mesoderm. k, l, Expression persists in the primitive streak and head process at the neural plate stage. m–r, β-Galactosidase staining of Cripto heterozygotes. m, n, Uniform staining in the epiblast before gastrulation. o, Sagittal section shows proximal–distal graded staining just before gastrulation. p, Early-streak stage embryo, and q, cross-section. r, Early neural-plate-stage embryo: note more intense staining at distal end of the primitive streak. In all panels, anterior faces to the left when anterior–posterior orientation can be identified; staging before primitive streak formation is approximate. Scale bars, 0.05 mm. A, anterior; D, distal; ep, epiblast; hp, head process; m, mesoderm; P, posterior; Pr, proximal; ps, primitive streak (bar denotes extent of streak); ve, visceral extra-embryonic endoderm.
Cripto is required for correct orientation of the anterior–posterior axis in the mouse embryo Nature volume 395, pages702–707 (1998) Published: 15 October 1998 https://www.nature.com/articles/27215
The Dynamics of Morphogenesis in the Early Mouse Embryo. Cold Spring Harbor Perspectives in Biology, 26 Jun 2014, 7(11):a015867 https://doi.org/10.1101/cshperspect.a015867 PMID: 24968703 PMCID: PMC4277506
Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse J. Rossant, P. Tam Published in Development 1 March 2009 Biology DOI:10.1242/dev.017178Corpus ID: 207151163
Vg1
Molecular mechanisms controlling the biogenesis of the TGF-β signal Vg1 PNAS October 16, 2023 120 (43) e2307203120 https://www.pnas.org/doi/10.1073/pnas.2307203120 The TGF-beta signals Nodal and Vg1 (Dvr1/Gdf3) play crucial roles in vertebrate development (1, 2), including the induction of mesendoderm and the generation of left-right asymmetry (3–17). For example, secreted Vg1-Nodal heterodimers induce a gradient of signaling that patterns the embryonic mesendoderm in zebrafish (10). Vg1-Nodal heterodimers exert their effects as ligands for a receptor complex that comprises Activin serine-threonine kinase receptors and an essential coreceptor called Oep (Tdgf1/CRIPTO) (18–20). Activated ligand-receptor complexes catalyze phosphorylation of Smad2 (pSmad2), which accumulates in the nucleus to induce the expression of mesendodermal genes (21).
中胚葉マーカー分子
Brachyury (TBXT (human), also T/Bra (mouse))
TBXT dose sensitivity and the decoupling of nascent mesoderm specification from EMT progression in 2D human gastruloids bioRxiv [Preprint]. 2023 Nov 9:2023.11.06.565933. [Version 2] doi: 10.1101/2023.11.06.565933
The T gene is necessary for normal mesodermal morphogenetic cell movements during gastrulation Development (1995) 121 (3): 877–886. the phenotype of homozygous mutant mouse embryos does not obviously correlate with an essential function for T during the early stages of gastrulation, since development rostral to the forelimb bud appears grossly normal. Only in more caudal trunk regions and in later embryos is the notochord missing and other mesodermal derivatives deficient or defective (Herrmann, 1992; Beddington et al., 1992; Rashbass et al., 1994). https://journals.biologists.com/dev/article/121/3/877/38504/The-T-gene-is-necessary-for-normal-mesodermal 機能的に重要そうなのにノックアウトマウスの表現型は非常にささやか。
A cell autonomous function of Brachyury in T/T embryonic stem cell chimaeras Nature volume 353, pages348–351 (1991) https://www.nature.com/articles/353348a0
Expression pattern of the mouse T gene and its role in mesoderm formation.Nature, 343(6259), 657–659. 10.1038/343657a0 Wilkinson D. G., Bhatt S., & Herrmann B. G. (1990). https://www.nature.com/articles/343657a0 有料
Effects of the brachyury (T) mutation on morphogenetic movement in the mouse embryo Dev Biol . 1981 Oct 30;87(2):242-8. doi: 10.1016/0012-1606(81)90147-0. 有料
抗体―薬物複合体開発の発展と現状 Drug Delivery System 34―1, 2019 https://www.jstage.jst.go.jp/article/dds/34/1/34_10/_pdf 抗体と薬物を共有結合で結合し、かつ、細胞内で、発現上昇している酵素などで切断するリンカーを組み入れる必要がある。
Monomethyl auristatin antibody and peptide drug conjugates for trimodal cancer chemo-radio-immunotherapy Published: 05 July 2022 https://www.nature.com/articles/s41467-022-31601-z
特許情報
http://datespriority:2009/03/06 Antibody drug conjugated that bind monomethyl auristatin e (mmae), compositions comprisimg the same and uses thereof https://pubchem.ncbi.nlm.nih.gov/patent/IL-214983-A0
Conjugate of monomethyl auristatin F and trastuzumab and its use for the treatment of cancer https://pubchem.ncbi.nlm.nih.gov/patent/US-9669106-B2
Yes, it is possible to make a patent claim that covers a method of using an antibody-drug conjugate (ADC) composed of a specific antibody (XX) and a specific drug payload (YY) for the treatment of a particular disease (ZZ). This type of patent claim is known as a “method of treatment” claim. In such claims, the inventors can specify the use of a particular composition (like an ADC) to treat a disease by detailing how the composition interacts with the disease target, the dosages, and other relevant therapeutic parameters.
Key Points About Method of Treatment Claims in ADC Patents:
Composition and Mechanism: These claims often describe how the antibody targets a specific antigen on cancer cells and how the cytotoxic drug component, once delivered, kills the cancer cells. For example, an ADC that combines antibody XX (which targets a specific receptor) and drug YY (a cytotoxic agent) could be claimed for the treatment of disease ZZ (such as a specific type of cancer).
Specificity of Antigen Target: You can claim that the antibody binds to a specific antigen that is overexpressed on diseased cells, such as CD33 in leukemia or HER2 in breast cancer. These antigen-targeting claims are critical because they define the ADC’s selectivity and therapeutic application.
Therapeutic Indications: The claim may specify the therapeutic indication, such as using the ADC for treating particular types of cancer, autoimmune diseases, or other conditions where the antibody target is expressed on disease-causing cells. For example, the patent could claim the method of using an ADC that targets HER2 for treating HER2-positive breast cancer Empower Innovation.
Dosage and Administration: These claims can also specify the dosage regimen, the route of administration (such as intravenous infusion), and how the therapy is applied in a clinical setting. The inclusion of such details helps to establish the uniqueness of the method of treatment claim.
Examples of Method of Treatment Claims:
HER2-Positive Cancer Treatment: A patent might claim the use of an ADC where the antibody targets the HER2 antigen and the cytotoxic drug is a maytansinoid, for treating HER2-positive cancers such as breast or gastric cancers.
Blood Cancer Treatment: Another patent might claim the use of an ADC targeting CD22 for the treatment of B-cell lymphomas.
Legal Considerations:
In some jurisdictions (such as the United States), method of treatment claims are allowed, but the specific rules may differ in other regions, such as the European Union, where method of treatment claims are subject to stricter scrutiny. In Europe, “Swiss-type” claims (use of a substance for the manufacture of a medicament) are often used instead.
In conclusion, making a patent claim that specifies using a particular antibody (XX) and drug (YY) for treating a particular disease (ZZ) is not only possible but a common strategy in the patenting of ADCs and other targeted therapies.
日本の事情
In Japan, method of treatment claims are generally not accepted. The Japanese Patent Office (JPO) follows the principle that medical treatment methods for humans cannot be patented. This includes methods of surgery, therapy, and diagnosis, as they are considered to fall under the scope of activities that should remain free from exclusive rights to ensure public health. This is similar to the approach taken by the European Patent Office (EPO)
However, there are alternative ways to protect innovations related to medical treatments:
1. Swiss-Type Claims (Use Claims):
While direct method of treatment claims are not allowed, Japanese law permits Swiss-type claims, which protect the use of a substance for the manufacture of a medicament for a specific therapeutic purpose. For example, instead of claiming “a method of treating cancer using ADCs,” a patent could claim “the use of ADC in the manufacture of a medicament for treating cancer.”
2. Product and Composition Claims:
You can claim the composition of the antibody-drug conjugate (ADC) itself. This would protect the ADC as a product, rather than its use in treating a disease. You can also claim the process for making the ADC or its use in a pharmaceutical composition, as long as the claim does not directly relate to a method of treatment.
3. Dosage Regimens:
Japan has allowed claims related to the dosage regimen of drugs, especially if it is new and inventive. For example, you may be able to patent a specific regimen for administering an ADC if it provides a novel therapeutic effect or improves patient outcomes.
Summary:
In Japan, method of treatment claims are not permissible, but alternatives like Swiss-type claims, product claims, or dosage regimen claims can be used to protect therapeutic innovations, including those involving antibody-drug conjugates.
Human eggs do not contain yolk proteins in the same way that bird or reptile eggs do. Here’s an explanation of the key differences:
Mammalian vs. Non-Mammalian Eggs
Non-Mammalian Eggs
Birds, reptiles, and many other non-mammalian species produce eggs with distinct yolks. These yolks are rich in proteins, lipids, vitamins, and minerals that provide nutrition to the developing embryo
In chicken eggs, for example, the yolk contains about 43% of the total egg protein and all of the egg’s fat
Human/Mammalian Eggs
Human eggs, like those of other mammals, have a fundamentally different structure:
No Distinct Yolk: Human eggs do not have a separate yolk compartment
Different Nutrient Source: Instead of relying on a yolk for nutrition, human embryos receive nutrients directly from the mother’s body through the placenta after implantation
Size Difference: Human eggs are much smaller than bird or reptile eggs, as they don’t need to store large amounts of nutrients.
Protein Content in Human Eggs
While human eggs don’t have yolk proteins per se, they do contain proteins that are crucial for early development:
Maternal Proteins: Human eggs contain various maternal proteins essential for fertilization and early embryonic development.
Cytoplasmic Components: The egg cytoplasm contains organelles and molecules necessary for initial cell divisions and embryo formation.
Evolutionary Perspective
The absence of yolk in human and other mammalian eggs is an evolutionary adaptation. Mammals have developed a more direct method of nourishing their offspring through placental connections, eliminating the need for a large, nutrient-rich yolk
In summary, while human eggs contain proteins vital for early development, they lack the specific yolk proteins found in the eggs of birds, reptiles, and other non-mammalian species.
内部細胞塊の細胞は最初はNanogとGATA6の両方の遺伝子を発現しています。それがしばらくすると、NanogかGATA6のどちらかを発現する細胞が入り混じった状態（いわゆる”salt and pepper”な状態）になります。
The salt-and-pepper pattern in mouse blastocysts is compatible with signaling beyond the nearest neighbors iScience Volume 26, Issue 11, 17 November 2023, 108106 (sciencedirect.com)
The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells Nature Communications volume 10, Article number: 1109 (2019) Published: 07 March 2019 https://www.nature.com/articles/s41467-019-09041-z
NANOG initiates epiblast fate through the coordination of pluripotency genes expression Nat Commun. 2022; 13: 3550; 2022 Jun 21. https://www.nature.com/articles/s41467-022-30858-8
NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis Journal of Experimental & Clinical Cancer Research volume 38, Article number: 416 (2019) Published: 16 October 2019 https://jeccr.biomedcentral.com/articles/10.1186/s13046-019-1429-z
FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst Development (2010) 137 (5): 715–724. https://doi.org/10.1242/dev.043471 01 March 2010
morula が inner cell mass と trohpoblastに分化する分子メカニズム
これが受精後に一様に見えた割球（桑実胚の時期）の最初の分化といえるでしょう。
Inner cell mass がEpiblastとPrimitive endodermに分化する分子メカニズム
2番目の大きな分化は、内部細胞塊が2種類にわかれることです。
下図は受精から卵割期のイベントと分子メカニズムがうまくまとめられています。
Volume 45, Issue 6, 18 June 2018, Pages 667-679 Journal home page for Developmental Cell Perspective Instructions for Assembling the Early Mammalian Embryo Developmental Cell https://www.sciencedirect.com/science/article/pii/S1534580718304052
Exp Cell Res. Author manuscript; available in PMC 2018 Sep 1. Published in final edited form as: Exp Cell Res. 2017 Sep 1; 358(1): 39–44. Published online 2017 Mar 31. https://doi.org/10.1016/j.yexcr.2017.03.061 PMCID: PMC5544570 NIHMSID: NIHMS866135 PMID: 28372972 Interplay Between Tight Junctions & Adherens Junctions https://europepmc.org/article/med/28372972#abstract
BRG1 Is Required for CDX2-Mediated Repression of oct4 Expression in Mouse Blastocysts https://www.researchgate.net/figure/Expression-and-localization-of-Cdx2-and-Oct4-in-Brg1-KD-blastocysts-A-ICC-analysis-of_fig7_44614272
As YAP and TAZ are transcriptional co-activators, they do not have DNA-binding domains. Instead, when inside the nucleus, they regulate gene expression through TEAD1-4 which are sequence-specific transcription factors that mediate the main transcriptional output of the Hippo pathway.The YAP/TAZ and TEAD interaction competitively inhibits and actively dissociates the TEAD/VGLL4 interaction which functions as a transcriptional repressor.
80560-7/asset/c406199d-b96b-4fea-9e41-d280ff70ea70/main.assets/gr1.jpg)
80560-7/asset/baa0b33b-7950-4e15-b02c-b80aaa387e9e/main.assets/gr2.jpg)
00417-1/asset/81432966-fc4a-450c-92e2-116d185449b6/main.assets/gr2.jpg)
00417-1/asset/dcd307b3-40eb-4e07-b401-f15cb71aed06/main.assets/gr5.jpg)
