المؤلفون: Janssen, Ralf¹ (AUTHOR) ralf.janssen@geo.uu.se, Budd, Graham E.¹ (AUTHOR)

المصدر: Frontiers in Zoology. 1/25/2024, Vol. 21 Issue 1, p1-21. 21p.

مصطلحات موضوعية: *GASTRULATION, *ENDODERM, *MESODERM, *EMBRYOLOGY, *GENE regulatory networks, *DROSOPHILA melanogaster

مستخلص: Background: Early during onychophoran development and prior to the formation of the germ band, a posterior tissue thickening forms the posterior pit. Anterior to this thickening forms a groove, the embryonic slit, that marks the anterior–posterior orientation of the developing embryo. This slit is by some authors considered the blastopore, and thus the origin of the endoderm, while others argue that the posterior pit represents the blastopore. This controversy is of evolutionary significance because if the slit represents the blastopore, then this would support the amphistomy hypothesis that suggests that a slit-like blastopore in the bilaterian ancestor evolved into protostomy and deuterostomy. Results: In this paper, we summarize our current knowledge about endoderm and mesoderm development in onychophorans and provide additional data on early endoderm- and mesoderm-determining marker genes such as Blimp, Mox, and the T-box genes. Conclusion: We come to the conclusion that the endoderm of onychophorans forms prior to the development of the embryonic slit, and thus that the slit is not the primary origin of the endoderm. It is thus unlikely that the embryonic slit represents the blastopore. We suggest instead that the posterior pit indeed represents the lips of the blastopore, and that the embryonic slit (and surrounding tissue) represents a morphologically superficial archenteron-like structure. We conclude further that both endoderm and mesoderm development are under control of conserved gene regulatory networks, and that many of the features found in arthropods including the model Drosophila melanogaster are likely derived. [ABSTRACT FROM AUTHOR]

المؤلفون: Oikonomou, Panagiotis¹, Cirne, Helena C.¹, Nerurkar, Nandan L.¹ nln2113@columbia.edu

المصدر: Development (09501991). Nov2023, Vol. 150 Issue 22, p1-12. 12p.

مصطلحات موضوعية: *MESODERM, *ENDODERM, *FIBROBLAST growth factors, *TISSUE mechanics, *CELL motility, *GASTRULATION, *PROTEOLYSIS

مستخلص: Although mechanical and biochemical descriptions of development are each essential, integration of upstream morphogenic cues with downstream tissue mechanics remains understudied during vertebrate morphogenesis. Here, we developed a two-dimensional chemo-mechanical model to investigate how mechanical properties of the endoderm and transport properties of fibroblast growth factor (FGF) regulate avian hindgut morphogenesis in a coordinated manner. Posterior endoderm cells convert a gradient of FGF ligands into a contractile force gradient, leading to a force imbalance that drives collective cell movements that elongate the forming hindgut tube. We formulated a 2D reaction-diffusionadvection model describing the formation of an FGF protein gradient as a result of posterior displacement of cells transcribing unstable Fgf8 mRNA during axis elongation, coupled with translation, diffusion and degradation of FGF protein. The endoderm was modeled as an active viscous fluid that generates contractile stresses in proportion to FGF concentration. With parameter values constrained by experimental data, the model replicates key aspects of hindgut morphogenesis, suggests that graded isotropic contraction is sufficient to generate large anisotropic cell movements, and provides new insight into how chemo-mechanical coupling across the mesoderm and endoderm coordinates hindgut elongation with axis elongation. [ABSTRACT FROM AUTHOR]

المؤلفون: Farkas, Karin^1,2 (AUTHOR) karin.farkas@sund.ku.dk, Ferretti, Elisabetta^1,3 (AUTHOR) elisabetta.ferretti@sund.ku.dk

المصدر: International Journal of Molecular Sciences. Jul2023, Vol. 24 Issue 14, p11366. 19p.

مصطلحات موضوعية: *ENDODERM, *GASTRULATION, *YOLK sac, *EMBRYOLOGY, *MESODERM, *CHORIONIC villi, *CELL populations

مستخلص: In vitro modeling of human peri-gastrulation development is a valuable tool for understanding embryogenetic mechanisms. The extraembryonic mesoderm (ExM) is crucial in supporting embryonic development by forming tissues such as the yolk sac, allantois, and chorionic villi. However, the origin of human ExM remains only partially understood. While evidence suggests a primitive endoderm (PrE) origin based on morphological findings, current in vitro models use epiblast-like cells. To address this gap, we developed a protocol to generate ExM-like cells from PrE-like cell line called naïve extraembryonic endoderm (nEnd). We identified the ExM-like cells by specific markers (LUM and ANXA1). Moreover, these in vitro-produced ExM cells displayed angiogenic potential on a soft matrix, mirroring their physiological role in vasculogenesis. By integrating single-cell RNA sequencing (scRNAseq) data, we found that the ExM-like cells clustered with the LUM/ANXA1-rich cell populations of the gastrulating embryo, indicating similarity between in vitro and ex utero cell populations. This study confirms the derivation of ExM from PrE and establishes a cell culture system that can be utilized to investigate ExM during human peri-gastrulation development, both in monolayer cultures and more complex models. [ABSTRACT FROM AUTHOR]

المؤلفون: Lide Su, Guofu Zhang, Lili Jiang, Chao Chi, Bing Bai, Kai Kang

المصدر: Stem Cell Research & Therapy, Vol 14, Iss 1, Pp 1-9 (2023)

مصطلحات موضوعية: C-Jun, Cardiac differentiation, Mesoderm, Endoderm, Embryonic body, Medicine (General), R5-920, Biochemistry, QD415-436

الوصف: Abstract Background Morbidity and mortality associated with cardiovascular diseases, such as myocardial infarction, stem from the inability of terminally differentiated cardiomyocytes to regenerate, and thus repair the damaged myocardial tissue structure. The molecular biological mechanisms behind the lack of regenerative capacity for those cardiomyocytes remains to be fully elucidated. Recent studies have shown that c-Jun serves as a cell cycle regulator for somatic cell fates, playing a key role in multiple molecular pathways, including the inhibition of cellular reprogramming, promoting angiogenesis, and aggravation of cardiac hypertrophy, but its role in cardiac development is largely unknown. This study aims to delineate the role of c-Jun in promoting early-stage cardiac differentiation. Methods The c-Jun gene in mouse embryonic stem cells (mESCs) was knocked out with CRISPR-Cas9, and the hanging drop method used to prepare the resulting embryoid bodies. Cardiac differentiation was evaluated up to 9 days after c-Jun knockout (ko) via immunofluorescence, flow cytometric, and qPCR analyses. Results Compared to the wild-type control group, obvious beating was observed among the c-Jun-ko mESCs after 6 days, which was also associated with significant increases in myocardial marker expression. Additionally, markers associated with mesoderm and endoderm cell layer development, essential for further differentiation of ESCs into cardiomyocytes, were also up-regulated in the c-Jun-ko cell group. Conclusions Knocking out c-Jun directs ESCs toward a meso-endodermal cell lineage fate, in turn leading to generation of beating myocardial cells. Thus, c-Jun plays an important role in regulating early cardiac cell development.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1757-6512Test

الوصول الحر: https://doaj.org/article/caa4c35feb004444b99753dbb7a788c0Test

المؤلفون: Jansen, Camden, Paraiso, Kitt D, Zhou, Jeff J, Blitz, Ira L, Fish, Margaret B, Charney, Rebekah M, Cho, Jin Sun, Yasuoka, Yuuri, Sudou, Norihiro, Bright, Ann Rose, Wlizla, Marcin, Veenstra, Gert Jan C, Taira, Masanori, Zorn, Aaron M, Mortazavi, Ali, Cho, Ken WY

المصدر: Cell Reports. 38(7)

مصطلحات موضوعية: Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Genetics, Biological Sciences, Human Genome, Stem Cell Research, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Animals, Chromatin, Consensus Sequence, DNA, Endoderm, Gastrulation, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Genomics, Mesoderm, Protein Binding, RNA, Transcription Factors, Transcription, Genetic, Xenopus, ATAC-seq, ChIP-seq, RNA-seq, cis-regulatory modules, endoderm, gene regulatory networks, linked self-organizing maps, mesoderm, multi-omic, Medical Physiology, Biological sciences

الوصف: Mesendodermal specification is one of the earliest events in embryogenesis, where cells first acquire distinct identities. Cell differentiation is a highly regulated process that involves the function of numerous transcription factors (TFs) and signaling molecules, which can be described with gene regulatory networks (GRNs). Cell differentiation GRNs are difficult to build because existing mechanistic methods are low throughput, and high-throughput methods tend to be non-mechanistic. Additionally, integrating highly dimensional data composed of more than two data types is challenging. Here, we use linked self-organizing maps to combine chromatin immunoprecipitation sequencing (ChIP-seq)/ATAC-seq with temporal, spatial, and perturbation RNA sequencing (RNA-seq) data from Xenopus tropicalis mesendoderm development to build a high-resolution genome scale mechanistic GRN. We recover both known and previously unsuspected TF-DNA/TF-TF interactions validated through reporter assays. Our analysis provides insights into transcriptional regulation of early cell fate decisions and provides a general approach to building GRNs using highly dimensional multi-omic datasets.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1ms272nqTest
https://escholarship.org/content/qt1ms272nq/qt1ms272nq.pdfTest

المؤلفون: Fagg, W, Liu, Naiyou, Braunschweig, Ulrich, Pereira de Castro, Karen, Chen, Xiaoting, Ditmars, Frederick, Widen, Steven, Donohue, John, Modis, Katalin, Russell, William, Fair, Jeffrey, Weirauch, Matthew, Blencowe, Benjamin, Garcia-Blanco, Mariano

المصدر: Nucleic Acids Research (NAR). 50(9)

مصطلحات موضوعية: Alternative Splicing, Cell Differentiation, Cell Lineage, Endoderm, Germ Layers, Heart, Humans, Mesoderm, RNA-Binding Proteins

الوصف: Alternative splicing is critical for development; however, its role in the specification of the three embryonic germ layers is poorly understood. By performing RNA-Seq on human embryonic stem cells (hESCs) and derived definitive endoderm, cardiac mesoderm, and ectoderm cell lineages, we detect distinct alternative splicing programs associated with each lineage. The most prominent splicing program differences are observed between definitive endoderm and cardiac mesoderm. Integrative multi-omics analyses link each program with lineage-enriched RNA binding protein regulators, and further suggest a widespread role for Quaking (QKI) in the specification of cardiac mesoderm. Remarkably, knockout of QKI disrupts the cardiac mesoderm-associated alternative splicing program and formation of myocytes. These changes arise in part through reduced expression of BIN1 splice variants linked to cardiac development. Mechanistically, we find that QKI represses inclusion of exon 7 in BIN1 pre-mRNA via an exonic ACUAA motif, and this is concomitant with intron removal and cleavage from chromatin. Collectively, our results uncover alternative splicing programs associated with the three germ lineages and demonstrate an important role for QKI in the formation of cardiac mesoderm.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/57t4d82bTest

المؤلفون: Lu, Vivian, Roy, Irena J, Torres, Alejandro, Joly, James H, Ahsan, Fasih M, Graham, Nicholas A, Teitell, Michael A

المصدر: Developmental Cell. 57(5)

مصطلحات موضوعية: Biochemistry and Cell Biology, Biological Sciences, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research - Embryonic - Human, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research, Regenerative Medicine, Underpinning research, 1.1 Normal biological development and functioning, Cell Differentiation, Cell Lineage, Endoderm, Germ Layers, Glutamine, Humans, Mesoderm, Pluripotent Stem Cells, auxotroph, cell fate, development, glutamine, nutrient, pluripotent stem cell, prototroph, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology

الوصف: Human pluripotent stem cells (hPSCs) can self-renew indefinitely or can be induced to differentiate. We previously showed that exogenous glutamine (Gln) withdrawal biased hPSC differentiation toward ectoderm and away from mesoderm. We revealed that, although all three germ lineages are capable of de novo Gln synthesis, only ectoderm generates sufficient Gln to sustain cell viability and differentiation, and this finding clarifies lineage fate restrictions under Gln withdrawal. Furthermore, we found that Gln acts as a signaling molecule for ectoderm that supersedes lineage-specifying cytokine induction. In contrast, Gln in mesoderm and endoderm is the preferred precursor of α-ketoglutarate without a direct signaling role. Our work raises a question about whether the nutrient environment functions directly in cell differentiation during development. Interestingly, transcriptome analysis of a gastrulation-stage human embryo shows that unique Gln enzyme-encoding gene expression patterns may also distinguish germ lineages in vivo. Together, our study suggests that intracellular Gln may help coordinate differentiation of the three germ layers.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/30z7b0sdTest

المؤلفون: Gadelha, Ana Indira Bezerra Barros, de Oliveira, Moacir Franco, de Sousa, Ana Caroline Freitas Caetano, Diniz, João Augusto Rodrigues Alves, Lopes, Igor Renno Guimarães, Fernandes, Bruno Caio Chaves, Pereira, Alexsandra Fernandes, de Moura, Carlos Eduardo Bezerra

المصدر: Zoomorphology; Sep2023, Vol. 142 Issue 3, p377-392, 16p

مصطلحات موضوعية: EPIBLAST, EMBRYOLOGY, MORPHOLOGY, MESODERM, ECTODERM, ENDODERM, AVIAN influenza

مستخلص: The greater rhea, Rhea americana, is a wild ratite of high scientific importance and significant and zootechnical value, especially considering the current development state of Brazilian poultry production, where research aimed at increasing the productivity of these animals has become extremely relevant. Studies concerning fetal attachments and embryonic development are paramount, as they can provide essential information concerning reproductive and nutritional animal management. However, a lack of information on greater rhea fetal morphology is noted. Therefore, the aim of the present study was to establish a standard model for fetal attachments in this species. Greater rhea eggs were incubated from 0 to 36 days, and macroscopic and microscopic embryonic attachment characterizations were performed. Histologically, all embryonic annexes exhibit germ layers, namely the ectoderm (outer layer), mesoderm (middle layer) and endoderm (inner layer). The findings indicate that greater rhea development patterns are similar to other birds. [ABSTRACT FROM AUTHOR]

: Copyright of Zoomorphology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Rodríguez Pizà, Ignasi

المساهمون: University/Department: Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut

مرشدي الرسالة: Izpisúa Belmonte, J. C., Raya Chamorro, Ángel, Veiga, Anna

المصدر: TDX (Tesis Doctorals en Xarxa)

مصطلحات موضوعية: Ectoderm, induced pluripotent stem cells, Haematopoietic stem cells, Cardiomyocyte, Blastocyst, Fanconi's anemia, Xeno-biòtics, Transgens, Teratoma, rebuig immunitari, Queratinòcits, Mesoderm, Fibroblasts, Endoderm, cèl·lules de pluripotència induïda, cèl·lules mare hematopoètiques, Cardiomiòcits, Blastocist, anemia de Fanconi, Keratinocytes, Immunological rejection, Xenobiotics

الوصف: Les cèl·lules mare embrionàries humanes (hESC) i més recentment les cèl·lules de pluripotència induïda (iPSC) representen una oportunitat sense precedents per al desenvolupament de noves estratègies terapèutiques per malalties degeneratives humanes. Així mateix, la possibilitat d'obtenir iPSC específiques de pacient obre la porta per l'establiment de models de malaltia genuïnament humans. Una de les limitacions que dificulta l'aplicació clínica de les cèl·lules pluripotents és que la seva obtenció es du a terme a l'actualitat amb medis i reactius que contenen fonts proteiques d'origen animal (xenobiòtics). Aquesta tesis contribueix al desenvolupament de protocols de derivació i de cultiu de hESC, que les apropa a la seva utilització clínica. A més hem desenvolupat estratègies basades en iPSC més segures i eficaces per al tractament de malalties humanes.

الوصف (مترجم): Human embryonic stem cells (hESC) and, more recently, induced pluripotent cells (iPSC) represent a new and unprecedented opportunity for the development of new therapeutic strategies for human degenerative diseases. The possibility to derive patient specific iPSC opens the door to he establishment of disease models exquisitely human. One of the limitation that, concretely, limits the clinic application of pluripotent cells is the fact that their derivation, currently, is obtained with media and reagents which contain animal proteic sources (xenobiotics). This thesis contributes to the development of protocols of derivation and culture of hESC that bring them closed to a clinical application. Moreover, we have developed iPSC-based strategies that are both safer and more effective for the treatment of human diseases.
Programa de doctorat en Biomedicina

وصف الملف: application/pdf

الوصول الحر: http://www.tdx.cat/TDX-0208111-142638Test
http://hdl.handle.net/10803/7227Test

المؤلفون: Schrankel, Catherine S.¹ (AUTHOR), Hamdoun, Amro¹ (AUTHOR) ahamdoun@ucsd.edu

المصدر: Developmental Biology. Apr2021, Vol. 472, p115-124. 10p.

مصطلحات موضوعية: *SMALL molecules, *ENDODERM, *EMBRYOS, *EMBRYOLOGY, *GERM cells, *MESODERM, *EFFLUX (Microbiology)

مستخلص: Directed intercellular movement of diverse small molecules, including metabolites, signal molecules and xenobiotics, is a key feature of multicellularity. Networks of small molecule transporters (SMTs), including several ATP Binding Cassette (ABC) transporters, are central to this process. While small molecule transporters are well described in differentiated organs, little is known about their patterns of expression in early embryogenesis. Here we report the pattern of ABC-type SMT expression and activity during the early development of sea urchins. Of the six major ABCs in this embryo (ABCB1, -B4, -C1, -C4, -C5 and -G2), three expression patterns were observed: 1) ABCB1 and ABCC1 are first expressed ubiquitously, and then become enriched in endoderm and ectoderm-derived structures. 2) ABCC4 and ABCC5 are restricted to a ring of mesoderm in the blastula and ABCC4 is later expressed in the coelomic pouches, the embryonic niche of the primordial germ cells. 3) ABCB4 and ABCG2 are expressed exclusively in endoderm-fated cells. Assays with fluorescent substrates and inhibitors of transporters revealed a ring of ABCC4 efflux activity emanating from ABCC4 + mesodermal cells. Similarly, ABCB1 and ABCB4 efflux activity was observed in the developing gut, prior to the onset of feeding. This study reveals the early establishment of unique territories of small molecule transport during embryogenesis. A pattern of ABCC4/C5 expression is consistent with signaling functions during gut invagination and germ line development, while a later pattern of ABCB1/B4 and ABCG2 is consistent with roles in the embryonic gut. This work provides a conceptual framework with which to examine the function and evolution of SMT networks and to define the specific developmental pathways that drive the expression of these genes. [Display omitted] • Regulated movement of small molecules is essential for both development and embryonic protection. • Little is known about spatiotemporal patterns of small molecule transporters in animal embryos. • We report a first of its kind map of transporter expression during embryogenesis of the sea urchin. • The results reveal novel domains of transport activity during endomesoderm differentiation. [ABSTRACT FROM AUTHOR]