The Experts below are selected from a list of 219 Experts worldwide ranked by ideXlab platform
Daisuke Saito - One of the best experts on this subject based on the ideXlab platform.
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epithelial to mesenchymal transition based morphogenesis of Dorsal Mesentery and gonad
Seminars in Cell & Developmental Biology, 2019Co-Authors: Takashi Yoshino, Daisuke SaitoAbstract:Abstract Dorsal Mesentery and gonad (ovary and testis) are formed in distinct regions of the body and have different characteristics. Recent studies using chicken embryos showed that progenitors of these two organs are derived from the coelomic lining region, a ventral part of the medial lateral plate mesoderm (M-LPM). Furthermore, both types of progenitors develop in a similar manner, concomitant with morphological changes termed the epithelial-to-mesenchymal transition (EMT). EMT processes in both Dorsal Mesentery and gonad formation are regulated by BMP signaling. Interestingly, EMT-based morphogenetic events occur repetitively at M-LPM specification before Dorsal mesenteric and gonadal formation, at ovary formation later in embryogenesis, and even during adult ovary repair. We review recent findings related to EMT-based morphogenesis and the governing molecular mechanisms, mainly in early Dorsal mesenteric and gonadal formation, as well as in their anlages and derivatives.
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Epithelial-to-mesenchymal transition–based morphogenesis of Dorsal Mesentery and gonad
Seminars in cell & developmental biology, 2018Co-Authors: Takashi Yoshino, Daisuke SaitoAbstract:Abstract Dorsal Mesentery and gonad (ovary and testis) are formed in distinct regions of the body and have different characteristics. Recent studies using chicken embryos showed that progenitors of these two organs are derived from the coelomic lining region, a ventral part of the medial lateral plate mesoderm (M-LPM). Furthermore, both types of progenitors develop in a similar manner, concomitant with morphological changes termed the epithelial-to-mesenchymal transition (EMT). EMT processes in both Dorsal Mesentery and gonad formation are regulated by BMP signaling. Interestingly, EMT-based morphogenetic events occur repetitively at M-LPM specification before Dorsal mesenteric and gonadal formation, at ovary formation later in embryogenesis, and even during adult ovary repair. We review recent findings related to EMT-based morphogenesis and the governing molecular mechanisms, mainly in early Dorsal mesenteric and gonadal formation, as well as in their anlages and derivatives.
Kjeld Møllgård - One of the best experts on this subject based on the ideXlab platform.
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The migration and loss of human primordial germ stem cells from the hind gut epithelium towards the gonadal ridge.
The International journal of developmental biology, 2012Co-Authors: Linn Salto Mamsen, Anne Grete Byskov, Christian Beltoft Brøchner, Kjeld MøllgårdAbstract:Human primordial germ cells (PGCs) can be recognized in the yolk sac wall, from 3-4 weeks post conception (wpc), in the hind gut epithelium from week 4 and in the gonadal area from early week 5. The objective of this study was to map the migration route of PGCs and elucidate the role of the nervous system in this process. Sixteen human specimens, 5-14 wpc obtained from legal abortions were included. On serial paraffin sections, PGCs were detected immunohistochemically by expression of OCT4 and c-Kit, nerve fibers by β-III-tubulin and stem cell factor (SCF) as a possible chemoattractive cue for PGC migration. PGCs were present in the hind gut epithelium, in the mesenchyme of the Dorsal Mesentery and in the developing gonadal ridge of 4-6 wpc embryos, prior to connections between the enteric and the sympathetic nervous system. From 6 wpc onwards, the PGCs travelled along the developing nerve fibers from the wall of the hind gut via the Dorsal Mesentery to the midline of the Dorsal wall and laterally into the gonads. Numerous PGCs were still present in the nervous system by 14 wpc. PGCs in 4-5 wpc embryos are suggested to leave the gut epithelium by EMT-like transition. SCF may facilitate further migration, but after establishment of connections between the enteric and sympathetic nervous systems. PGCs follow sympathetic nerve fibers towards the gonads. PGCs failing to exit the nerve branches at the gonadal site, may continue along the sympathetic trunk ending up in other organs where they may form germ cell tumors if not eliminated by apoptosis.
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human primordial germ cells migrate along nerve fibers and schwann cells from the Dorsal hind gut Mesentery to the gonadal ridge
Molecular Human Reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, Yding C Andersen, P E Hoyer, Ase Jespersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic nerve fibers and primordial germ cells (PGCs) along their migratory route from the Dorsal Mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic nerve fibers in the Dorsal Mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for b III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these nerve fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic nerve fibers with the majority adjacent to the most peripheral fibers (close to Schwann cells). We also show that both nerve fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic nerve fibers from the Dorsal Mesentery to the developing gonad where they are delivered via a fine nerve plexus.
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Human primordial germ cells migrate along nerve fibers and Schwann cells from the Dorsal hind gut Mesentery to the gonadal ridge
Molecular human reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, P E Hoyer, Ase Jespersen, C. Yding Andersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic nerve fibers and primordial germ cells (PGCs) along their migratory route from the Dorsal Mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic nerve fibers in the Dorsal Mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for beta III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these nerve fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic nerve fibers with the majority adjacent to the most peripheral fibers (close to Schwann cells). We also show that both nerve fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic nerve fibers from the Dorsal Mesentery to the developing gonad where they are delivered via a fine nerve plexus.
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Stem cell factor and c-Kit in human primordial germ cells and fetal ovaries.
Molecular and Cellular Endocrinology, 2005Co-Authors: P E Hoyer, Anne Grete Byskov, Kjeld MøllgårdAbstract:The distribution of the tyrosine kinase receptor c-Kit and its ligand stem cell factor (SCF) was evaluated by immunohistochemistry in primordial germ cells (PGCs) and human embryonic gonads during weeks 5-8 of prenatal life, and fetal ovaries during weeks 9-36 of prenatal life. Distinct c-Kit and SCF staining was present in primordial germ cells in the wall of the hindgut and in the Dorsal Mesentery, particularly on level with the 10th thoracic columnar segment. Several PGCs were in close contact with c-Kit-negative but SCF-positive autonomic nerve fibers of the Dorsal Mesentery. Many fibroblasts and mesothelial cells of the Dorsal Mesentery were clearly stained for SCF, but not for c-Kit. Prominent c-Kit and SCF staining was present in germ cells of the embryonic gonadal anlage and in oogonia during further ovarian development. However, oocytes were either unstained or faintly stained for SCF. Oocytes not yet enclosed in follicles or present in primordial follicles were either unstained or exhibited faint cytoplasmic c-Kit staining, whereas oocytes of growing preantral follicles again showed distinct cell membrane staining which decreased during further follicular growth. Theca cells did not stain for c-Kit. Some pregranulosa cells and the first formed granulosa cells of primordial follicles were c-Kit stained. Granulosa cells of other follicles were not c-Kit stained. In the inner part of the cortex, SCF immunolabeling was detected in some pregranulosa cells surrounding cords containing germ cells and involved in formation of primordial follicles. Granulosa cells of primordial and growing follicles, including medium-sized antral follicles also revealed SCF staining. In conclusion, this first report on SCF in human PGCs and embryonic and fetal ovaries together with the c-Kit data lend substantial countenance to the notion that c-Kit and SCF play important roles during ascent of primordial germ cells towards the gonadal anlage, and during oogenesis and folliculogenesis in the human fetal ovary. We suggest that both autocrine and paracrine mechanisms are involved in the proposed anti-apoptotic effect of the c-Kit/SCF duet while PGCs are present in the Dorsal Mesentery. The SCF-positive autonomic nerve fibers of the Dorsal Mesentery, mesothelial cells and fibroblasts may nurse and perhaps guide PGCs during their ascent.
Anne Grete Byskov - One of the best experts on this subject based on the ideXlab platform.
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The migration and loss of human primordial germ stem cells from the hind gut epithelium towards the gonadal ridge.
The International journal of developmental biology, 2012Co-Authors: Linn Salto Mamsen, Anne Grete Byskov, Christian Beltoft Brøchner, Kjeld MøllgårdAbstract:Human primordial germ cells (PGCs) can be recognized in the yolk sac wall, from 3-4 weeks post conception (wpc), in the hind gut epithelium from week 4 and in the gonadal area from early week 5. The objective of this study was to map the migration route of PGCs and elucidate the role of the nervous system in this process. Sixteen human specimens, 5-14 wpc obtained from legal abortions were included. On serial paraffin sections, PGCs were detected immunohistochemically by expression of OCT4 and c-Kit, nerve fibers by β-III-tubulin and stem cell factor (SCF) as a possible chemoattractive cue for PGC migration. PGCs were present in the hind gut epithelium, in the mesenchyme of the Dorsal Mesentery and in the developing gonadal ridge of 4-6 wpc embryos, prior to connections between the enteric and the sympathetic nervous system. From 6 wpc onwards, the PGCs travelled along the developing nerve fibers from the wall of the hind gut via the Dorsal Mesentery to the midline of the Dorsal wall and laterally into the gonads. Numerous PGCs were still present in the nervous system by 14 wpc. PGCs in 4-5 wpc embryos are suggested to leave the gut epithelium by EMT-like transition. SCF may facilitate further migration, but after establishment of connections between the enteric and sympathetic nervous systems. PGCs follow sympathetic nerve fibers towards the gonads. PGCs failing to exit the nerve branches at the gonadal site, may continue along the sympathetic trunk ending up in other organs where they may form germ cell tumors if not eliminated by apoptosis.
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human primordial germ cells migrate along nerve fibers and schwann cells from the Dorsal hind gut Mesentery to the gonadal ridge
Molecular Human Reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, Yding C Andersen, P E Hoyer, Ase Jespersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic nerve fibers and primordial germ cells (PGCs) along their migratory route from the Dorsal Mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic nerve fibers in the Dorsal Mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for b III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these nerve fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic nerve fibers with the majority adjacent to the most peripheral fibers (close to Schwann cells). We also show that both nerve fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic nerve fibers from the Dorsal Mesentery to the developing gonad where they are delivered via a fine nerve plexus.
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Human primordial germ cells migrate along nerve fibers and Schwann cells from the Dorsal hind gut Mesentery to the gonadal ridge
Molecular human reproduction, 2010Co-Authors: Kjeld Møllgård, Melissa C Lutterodt, P E Hoyer, Ase Jespersen, C. Yding Andersen, Anne Grete ByskovAbstract:The aim of this study was to investigate the spatiotemporal development of autonomic nerve fibers and primordial germ cells (PGCs) along their migratory route from the Dorsal Mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic nerve fibers in the Dorsal Mesentery, the pre-aortic and para-aortic plexuses and in the gonadal ridge were stained for beta III tubulin, neuron specific enolase and the glia fibrillary acidic protein. Electron microscopy demonstrated the presence of neurofilaments and neurotubules in these nerve fibers and their intimate contact with PGCs. PGCs expressed GAGE, MAGE-A4, OCT4 and c-Kit. Serial paraffin sections showed that most PGCs were located inside bundles of autonomic nerve fibers with the majority adjacent to the most peripheral fibers (close to Schwann cells). We also show that both nerve fibers and PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic nerve fibers from the Dorsal Mesentery to the developing gonad where they are delivered via a fine nerve plexus.
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Stem cell factor and c-Kit in human primordial germ cells and fetal ovaries.
Molecular and Cellular Endocrinology, 2005Co-Authors: P E Hoyer, Anne Grete Byskov, Kjeld MøllgårdAbstract:The distribution of the tyrosine kinase receptor c-Kit and its ligand stem cell factor (SCF) was evaluated by immunohistochemistry in primordial germ cells (PGCs) and human embryonic gonads during weeks 5-8 of prenatal life, and fetal ovaries during weeks 9-36 of prenatal life. Distinct c-Kit and SCF staining was present in primordial germ cells in the wall of the hindgut and in the Dorsal Mesentery, particularly on level with the 10th thoracic columnar segment. Several PGCs were in close contact with c-Kit-negative but SCF-positive autonomic nerve fibers of the Dorsal Mesentery. Many fibroblasts and mesothelial cells of the Dorsal Mesentery were clearly stained for SCF, but not for c-Kit. Prominent c-Kit and SCF staining was present in germ cells of the embryonic gonadal anlage and in oogonia during further ovarian development. However, oocytes were either unstained or faintly stained for SCF. Oocytes not yet enclosed in follicles or present in primordial follicles were either unstained or exhibited faint cytoplasmic c-Kit staining, whereas oocytes of growing preantral follicles again showed distinct cell membrane staining which decreased during further follicular growth. Theca cells did not stain for c-Kit. Some pregranulosa cells and the first formed granulosa cells of primordial follicles were c-Kit stained. Granulosa cells of other follicles were not c-Kit stained. In the inner part of the cortex, SCF immunolabeling was detected in some pregranulosa cells surrounding cords containing germ cells and involved in formation of primordial follicles. Granulosa cells of primordial and growing follicles, including medium-sized antral follicles also revealed SCF staining. In conclusion, this first report on SCF in human PGCs and embryonic and fetal ovaries together with the c-Kit data lend substantial countenance to the notion that c-Kit and SCF play important roles during ascent of primordial germ cells towards the gonadal anlage, and during oogenesis and folliculogenesis in the human fetal ovary. We suggest that both autocrine and paracrine mechanisms are involved in the proposed anti-apoptotic effect of the c-Kit/SCF duet while PGCs are present in the Dorsal Mesentery. The SCF-positive autonomic nerve fibers of the Dorsal Mesentery, mesothelial cells and fibroblasts may nurse and perhaps guide PGCs during their ascent.
Takashi Yoshino - One of the best experts on this subject based on the ideXlab platform.
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epithelial to mesenchymal transition based morphogenesis of Dorsal Mesentery and gonad
Seminars in Cell & Developmental Biology, 2019Co-Authors: Takashi Yoshino, Daisuke SaitoAbstract:Abstract Dorsal Mesentery and gonad (ovary and testis) are formed in distinct regions of the body and have different characteristics. Recent studies using chicken embryos showed that progenitors of these two organs are derived from the coelomic lining region, a ventral part of the medial lateral plate mesoderm (M-LPM). Furthermore, both types of progenitors develop in a similar manner, concomitant with morphological changes termed the epithelial-to-mesenchymal transition (EMT). EMT processes in both Dorsal Mesentery and gonad formation are regulated by BMP signaling. Interestingly, EMT-based morphogenetic events occur repetitively at M-LPM specification before Dorsal mesenteric and gonadal formation, at ovary formation later in embryogenesis, and even during adult ovary repair. We review recent findings related to EMT-based morphogenesis and the governing molecular mechanisms, mainly in early Dorsal mesenteric and gonadal formation, as well as in their anlages and derivatives.
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Epithelial-to-mesenchymal transition–based morphogenesis of Dorsal Mesentery and gonad
Seminars in cell & developmental biology, 2018Co-Authors: Takashi Yoshino, Daisuke SaitoAbstract:Abstract Dorsal Mesentery and gonad (ovary and testis) are formed in distinct regions of the body and have different characteristics. Recent studies using chicken embryos showed that progenitors of these two organs are derived from the coelomic lining region, a ventral part of the medial lateral plate mesoderm (M-LPM). Furthermore, both types of progenitors develop in a similar manner, concomitant with morphological changes termed the epithelial-to-mesenchymal transition (EMT). EMT processes in both Dorsal Mesentery and gonad formation are regulated by BMP signaling. Interestingly, EMT-based morphogenetic events occur repetitively at M-LPM specification before Dorsal mesenteric and gonadal formation, at ovary formation later in embryogenesis, and even during adult ovary repair. We review recent findings related to EMT-based morphogenesis and the governing molecular mechanisms, mainly in early Dorsal mesenteric and gonadal formation, as well as in their anlages and derivatives.
Natasza A Kurpios - One of the best experts on this subject based on the ideXlab platform.
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Chromatin architecture of the Pitx2 locus requires CTCF and Pitx2 dependent asymmetry that mirrors embryonic gut laterality
Cell reports, 2015Co-Authors: Ian C Welsh, James F Martin, Hojoong Kwak, Frances L. Chen, Melissa Werner, Lindsay S. Shopland, Charles G. Danko, John T. Lis, Min Zhang, Natasza A KurpiosAbstract:Expression of Pitx2 on the left side of the embryo patterns left-right (LR) organs including the Dorsal Mesentery (DM), whose asymmetric cell behavior directs gut looping. Despite the importance of organ laterality, chromatin-level regulation of Pitx2 remains undefined. Here, we show that genes immediately neighboring Pitx2 in chicken and mouse, including a long noncoding RNA (Pitx2 locus-asymmetric regulated RNA or Playrr), are expressed on the right side and repressed by Pitx2. CRISPR/Cas9 genome editing of Playrr, 3D fluorescent in situ hybridization (FISH), and variations of chromatin conformation capture (3C) demonstrate that mutual antagonism between Pitx2 and Playrr is coordinated by asymmetric chromatin interactions dependent on Pitx2 and CTCF. We demonstrate that transcriptional and morphological asymmetries driving gut looping are mirrored by chromatin architectural asymmetries at the Pitx2 locus. We propose a model whereby Pitx2 auto-regulation directs chromatin topology to coordinate LR transcription of this locus essential for LR organogenesis.
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The left-right Pitx2 pathway drives organ-specific arterial and lymphatic development in the intestine.
Developmental cell, 2014Co-Authors: Aparna Mahadevan, Ian C Welsh, Aravind Sivakumar, Rusty Lansford, David W. Gludish, Abigail R. Shilvock, Drew M. Noden, David Huss, Natasza A KurpiosAbstract:Summary The Dorsal Mesentery (DM) is the major conduit for blood and lymphatic vessels in the gut. The mechanisms underlying their morphogenesis are challenging to study and remain unknown. Here we show that arteriogenesis in the DM begins during gut rotation and proceeds strictly on the left side, dependent on the Pitx2 target gene Cxcl12 . Although competent Cxcr4 -positive angioblasts are present on the right, they fail to form vessels and progressively emigrate. Surprisingly, gut lymphatics also initiate in the left DM and arise only after—and dependent on—arteriogenesis, implicating arteries as drivers of gut lymphangiogenesis. Our data begin to unravel the origin of two distinct vascular systems and demonstrate how early left-right molecular asymmetries are translated into organ-specific vascular patterns. We propose a dual origin of gut lymphangiogenesis in which prior arterial growth is required to initiate local lymphatics that only subsequently connect to the vascular system.
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Listen to your Dorsal Mesentery: Asymmetric gut rotation is driven by the Dorsal Mesentery and Pitx2
Molecular Reproduction and Development, 2012Co-Authors: Natasza A KurpiosAbstract:The generation of organ asymmetries is a fundamental aspect of embryonic development. Most organs develop with a characteristic left-right (L-R) asymmetry that is critical to normal function and to coordinated organ development. The small intestine is a simple, tubular structure that undergoes a highly conserved, counter-clockwise rotation that is initiated by expression of the early L-R symmetry-breaking transcription factor Pitx2. Gross expression reveals surprising symmetry from the Dorsal perspective of a chicken embryo (whole-mount in situ). Yet closer examination of areas where symmetry will be first broken shows the bias. For example, Pitx2 is expressed on the left side of the Dorsal Mesentery (background, color-inverted image of an in situ hybridization; white indicates more intense expression) and is necessary and sufficient to produce the leftward tilt. Although Pitx2 is a master regulator of L-R organ development, there are currently no targets of Pitx2 known that are relevant to asymmetric morphogenesis.
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the chirality of gut rotation derives from left right asymmetric changes in the architecture of the Dorsal Mesentery
Developmental Cell, 2008Co-Authors: Nicole M Davis, Natasza A Kurpios, Jerome Gros, James F Martin, Clifford J TabinAbstract:We have investigated the structural basis by which the counterclockwise direction of the amniote gut is established. The chirality of midgut looping is determined by left-right asymmetries in the cellular architecture of the Dorsal Mesentery, the structure that connects the primitive gut tube to the body wall. The mesenchymal cells of the Dorsal Mesentery are more condensed on the left side than on the right and, additionally, the overlying epithelium on the left side exhibits a columnar morphology, in contrast to a cuboidal morphology on the right. These properties are instructed by a set of transcription factors: Pitx2 and Isl1 specifically expressed on the left side, and Tbx18 expressed on the right, regulated downstream of the secreted protein Nodal which is present exclusively on the left side. The resultant differences in cellular organization cause the Mesentery to assume a trapezoidal shape, tilting the primitive gut tube leftward.
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The direction of gut looping is established by changes in the extracellular matrix and in cell:cell adhesion
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Natasza A Kurpios, Nicole M Davis, James F Martin, Marta Ibañes, Wei Lui, Tamar C. Katz, Juan Carlos Izpisua Belmonte, Clifford J TabinAbstract:The counterclockwise coiling of the intestines is initiated by a leftward tilt of the primitive gut tube, imparted by left–right asymmetries in the architecture of the Dorsal Mesentery. In silico analysis suggests that this is achieved by synergistic changes in its epithelium and mesenchyme. Within the mesenchymal compartment, cells are more densely packed on the left than on the right. In silico results indicate that this property can result from asymmetries in both extracellular matrix (ECM) and cell:cell adhesion. We find that the Dorsal Mesentery ECM is indeed left–right asymmetric and moreover that the adhesion molecule N-cadherin is expressed exclusively on the left side. These asymmetries are regulated by the asymmetrically expressed transcription factors Pitx2 and Isl1. Functional studies demonstrate that N-cadherin acts upstream of the changes in the ECM and is both necessary and sufficient to explain the asymmetric packing of the mesenchymal cells.