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Genesis (New York, N.Y. : 2000) May 2014Insufficiency of surfactants is a core factor in respiratory distress syndrome, which causes apnea and neonatal death, particularly in preterm infants. Surfactant...
Insufficiency of surfactants is a core factor in respiratory distress syndrome, which causes apnea and neonatal death, particularly in preterm infants. Surfactant proteins are secreted by alveolar type II cells in the lung epithelium, the differentiation of which is regulated by Fgf10 elaborated by the adjacent mesenchyme. However, the molecular regulation of mesenchymal Fgf10 during lung development has not been fully understood. Here, we show that Pbx1, a homeodomain transcription factor, is required in the lung mesenchyme for the expression of Fgf10. Mouse embryos lacking Pbx1 in the lung mesenchyme show compact terminal saccules and perinatal lethality with failure of postnatal alveolar expansion. Mutant embryos had severely reduced expression of Fgf10 and surfactant genes (Spa, Spb, Spc, and Spd) that are essential for alveolar expansion for gas exchange at birth. Molecularly, Pbx1 directly binds to the Fgf10 promoter and cooperates with Meis and Hox proteins to transcriptionally activate Fgf10. Our results thus show how Pbx1 controls Fgf10 in the developing lung.
Topics: Animals; Female; Fibroblast Growth Factor 10; Gene Expression Regulation, Developmental; Homeodomain Proteins; Lung; Mesoderm; Mice; Mice, Transgenic; Pre-B-Cell Leukemia Transcription Factor 1; Pregnancy; Promoter Regions, Genetic; Transcription Factors
PubMed: 24591256
DOI: 10.1002/dvg.22764 -
Seminars in Cell & Developmental Biology Apr 2007Salivary glands provide an excellent model for the study of epithelial-mesenchymal interactions and branching morphogenesis. This review will discuss the anatomy of... (Review)
Review
Salivary glands provide an excellent model for the study of epithelial-mesenchymal interactions and branching morphogenesis. This review will discuss the anatomy of different types of glands, in a range of different organisms. Then, concentrating on the mouse submandibular gland, the stages of salivary gland development will be reviewed and the relative role of the mesenchyme and the epithelium will be discussed. Finally, the genes thought to play a role in development of the glands from initiation to differentiation will be reviewed.
Topics: Animals; Epithelium; Mesoderm; Mice; Models, Biological; Morphogenesis; Organogenesis; Salivary Glands
PubMed: 17336109
DOI: 10.1016/j.semcdb.2007.01.006 -
Developmental Cell Jan 2018Many tissues fold into complex shapes during development. Controlling this process in vitro would represent an important advance for tissue engineering. We use...
Many tissues fold into complex shapes during development. Controlling this process in vitro would represent an important advance for tissue engineering. We use embryonic tissue explants, finite element modeling, and 3D cell-patterning techniques to show that mechanical compaction of the extracellular matrix during mesenchymal condensation is sufficient to drive tissue folding along programmed trajectories. The process requires cell contractility, generates strains at tissue interfaces, and causes patterns of collagen alignment around and between condensates. Aligned collagen fibers support elevated tensions that promote the folding of interfaces along paths that can be predicted by modeling. We demonstrate the robustness and versatility of this strategy for sculpting tissue interfaces by directing the morphogenesis of a variety of folded tissue forms from patterns of mesenchymal condensates. These studies provide insight into the active mechanical properties of the embryonic mesenchyme and establish engineering strategies for more robustly directing tissue morphogenesis ex vivo.
Topics: Animals; Chick Embryo; Extracellular Matrix; Finite Element Analysis; Intestines; Mesoderm; Mice; Skin; Tissue Engineering
PubMed: 29290586
DOI: 10.1016/j.devcel.2017.12.004 -
Ontogenez 1989A series of reciprocal interactions between epithelial and mesenchymal tissues control the morphogenesis and cell differentiation in the developing tooth. The molecular... (Review)
Review
A series of reciprocal interactions between epithelial and mesenchymal tissues control the morphogenesis and cell differentiation in the developing tooth. The molecular mechanisms operating in these interactions are, however, unknown at present. Structural components of the extracellular matrix (ECM) affect cellular behavior in the embryo and appear to be involved also in these regulatory processes. The ECM molecules exert their effects on cells through binding to specific matrix receptors on the cell surface. This review article summarizes our findings on the distribution patterns during tooth development of the ECM glycoproteins, fibronectin and tenascin, and of the cell surface proteoglycan, syndecan, which functions as a receptor for interstitial matrix. Based on the observed changes in these distribution patterns and on experimental evidence, roles for these molecules in epithelial-mesenchymal interactions during tooth development are suggested. Fibronectin and tenascin are enriched in the dental basement membrane at the time of odontoblast differentiation. These matrix glycoproteins may be involved in the cell-matrix interaction which controls differentiation of the dental mesenchymal cells into odontoblasts. Tenascin and syndecan are accumulated in the dental mesenchyme during bud stage of development. We have shown in tissue recombination experiments that the presumptive dental epithelium induces the expression of tenascin and syndecan in mesenchyme. We suggest that these molecules are involved in cell-matrix interactions, which regulate mesenchymal cell condensation during the earliest stages of tooth morphogenesis.
Topics: Basement Membrane; Cell Adhesion Molecules, Neuronal; Cell Differentiation; Epithelial Cells; Epithelium; Extracellular Matrix; Humans; Membrane Glycoproteins; Mesoderm; Morphogenesis; Odontoblasts; Odontogenesis; Proteoglycans; Surface Properties; Syndecans; Tenascin
PubMed: 2477776
DOI: No ID Found -
Differentiation; Research in Biological... Jul 2008This review summarizes the history of research on mesenchymal-epithelial interactions in prostatic development from the first studies in 1970 to the present. From this... (Review)
Review
This review summarizes the history of research on mesenchymal-epithelial interactions in prostatic development from the first studies in 1970 to the present. From this study we have learned that prostatic development requires a reciprocal interaction between epithelium and mesenchyme in which urogenital sinus mesenchyme induces and patterns epithelial development and differentiation, while developing prostatic epithelium induces and patterns mesenchymal differentiation into smooth muscle and other resident cell types in the stroma. Prostatic development requires androgen action mediated by the androgen receptor (AR). Through analysis of tissue recombinants composed of wild-type and AR-null epithelium and mesenchyme, we have learned that many "androgenic effects" on prostatic epithelium do not require epithelial AR, but instead are elicited by the paracrine action of AR-positive mesenchyme. Present and future studies reviewed in this issue deal with the molecular mechanisms in this developmental communication between epithelium and mesenchyme.
Topics: Androgens; Animals; Epithelium; Humans; Male; Mesoderm; Mice; Prostate
PubMed: 18557761
DOI: 10.1111/j.1432-0436.2008.00290.x -
Cell and Tissue Research Jun 2017During development, the gastrointestinal (GI) tract arises from a primary tube composed of mesoderm and endoderm. The mesoderm gives rise to the digestive mesenchyme,...
During development, the gastrointestinal (GI) tract arises from a primary tube composed of mesoderm and endoderm. The mesoderm gives rise to the digestive mesenchyme, which in turn differentiates into multiple tissues, namely the submucosa, the interstitial cells of Cajal and the smooth muscle cells (SMCs). Concomitant with these early patterning events, the primitive GI tract is colonized by vagal enteric neural crest-derived cells (vENCDCs), a population of cells that gives rise to the enteric nervous system, the intrinsic innervation of the GI tract. Reciprocal neuro-mesenchymal interactions are essential for the coordinated development of GI musculature. The aim of this study is to examine and compare the kinetics of mesenchymal cell differentiation into SMCs along the anterior-posterior axis to the pattern of vENCDCs migration using whole-mount in situ hybridization and paraffin section immunofluorescence analyses on chick embryonic GI tracts from E4-Stage 23 to E7-Stages 30-31. We confirmed that gastric and pre-umbilical intestine mesenchyme differentiation into SMCs occurs after vENCDCs colonization. However, we found that colonic and post-umbilical intestine mesenchyme differentiation occurs before vENCDCs colonization. These findings suggest that regional-specific mechanisms are involved in the mesenchyme differentiation into SMCs along the GI anterior-posterior axis.
Topics: Animals; Body Patterning; Cell Differentiation; Chick Embryo; Colon; Enteric Nervous System; Intestines; Mesoderm; Muscle, Smooth; Neural Crest; Stomach
PubMed: 28197779
DOI: 10.1007/s00441-017-2577-0 -
BioTechniques Jul 2013Current protocols for separating adult intestinal epithelial cells from the underlying muscular and mesenchymal tissues typically involve extended incubations, harsh...
Current protocols for separating adult intestinal epithelial cells from the underlying muscular and mesenchymal tissues typically involve extended incubations, harsh mechanical treatment, and exposure to either proteases or chelating agents. The drawbacks of these approaches include fragmentation, contamination with other cell types, reduced viability, and under-representation of crypt cells. Here we describe a gentle procedure that allows harvesting of pure, fully viable sheets of murine intestinal epithelium, with intact crypts and villi, without enzymes or EDTA. The mesenchyme retains intact villus core projections, is virtually free from epithelial cells, and can be cultured in vitro.
Topics: Animals; Histological Techniques; Intestinal Mucosa; Mesoderm; Mice; Mice, Transgenic
PubMed: 23834385
DOI: 10.2144/000114055 -
Mechanisms of Development 2008We have analysed the contributions of neural crest and mesoderm to mammalian craniofacial mesenchyme and its derivatives by cell lineage tracing experiments in mouse...
We have analysed the contributions of neural crest and mesoderm to mammalian craniofacial mesenchyme and its derivatives by cell lineage tracing experiments in mouse embryos, using the permanent genetic markers Wnt1-cre for neural crest and Mesp1-cre for mesoderm, combined with the Rosa26 reporter. At the end of neural crest cell migration (E9.5) the two patterns are reciprocal, with a mutual boundary just posterior to the eye. Mesodermal cells expressing endothelial markers (angioblasts) are found not to respect this boundary; they are associated with the migrating neural crest from the 5-somite stage, and by E9.5 they form a pre-endothelial meshwork throughout the cranial mesenchyme. Mesodermal cells of the myogenic lineage also migrate with neural crest cells, as the branchial arches form. By E17.5 the neural crest-mesoderm boundary in the subectodermal mesenchyme becomes out of register with that of the underlying skeletogenic layer, which is between the frontal and parietal bones. At E13.5 the primordia of these bones lie basolateral to the brain, extending towards the vertex of the skull during the following 4-5 days. We used DiI labelling of the bone primordia in ex-utero E13.5 embryos to distinguish between two possibilities for the origin of the frontal and parietal bones: (1) recruitment from adjacent connective tissue or (2) proliferation of the original primordia. The results clearly demonstrated that the bone primordia extend vertically by intrinsic growth, without detectable recruitment of adjacent mesenchymal cells.
Topics: Animals; Cell Lineage; Cell Movement; Connective Tissue; Endothelial Cells; Frontal Bone; Mammals; Mesoderm; Mice; Muscle Development; Neural Crest; Parietal Bone; Skull; beta-Galactosidase
PubMed: 18617001
DOI: 10.1016/j.mod.2008.06.007 -
Development (Cambridge, England) Aug 2011The digestive tract epithelium and its adjoining mesenchyme undergo coordinated patterning and growth during development. The signals they exchange in the process are...
The digestive tract epithelium and its adjoining mesenchyme undergo coordinated patterning and growth during development. The signals they exchange in the process are not fully characterized but include ligands of the Hedgehog (Hh) family, which originate in the epithelium and are necessary for mesenchymal cells to expand in number and drive elongation of the developing gut tube. The Notch signaling pathway has known requirements in fetal and adult intestinal epithelial progenitors. We detected Notch pathway activity in the embryonic gut mesenchyme and used conditional knockout mice to study its function. Selective disruption of the Notch effector gene RBP-Jκ (Rbpj) in the mesenchyme caused progressive loss of subepithelial fibroblasts and abbreviated gut length, revealing an unexpected requirement in this compartment. Surprisingly, constitutive Notch activity also induced rapid mesenchymal cell loss and impaired organogenesis, probably resulting from increased cell death and suggesting the need for a delicate balance in Notch signaling. Because digestive tract anomalies in mouse embryos with excess Notch activity phenocopy the absence of Hh signaling, we postulated that endodermal Hh restrains mesenchymal Notch pathway activity. Indeed, Hh-deficient embryos showed Notch overactivity in their defective gut mesenchyme and exposure to recombinant sonic hedgehog could override Notch-induced death of cultured fetal gut mesenchymal cells. These results reveal unexpected interactions between prominent signals in gastrointestinal development and provide a coherent explanation for Hh requirements in mesenchymal cell survival and organ growth.
Topics: Animals; Cell Proliferation; Female; Gastrointestinal Tract; Gene Expression Regulation, Developmental; Hedgehog Proteins; Male; Mesoderm; Mice; Mice, Knockout; Mice, Transgenic; Receptors, Notch; Signal Transduction
PubMed: 21750033
DOI: 10.1242/dev.066233 -
Journal of Visualized Experiments : JoVE Apr 2013Orofacial clefts are the most frequent craniofacial defects, which affect 1.5 in 1,000 newborns worldwide. Orofacial clefting is caused by abnormal facial development....
Orofacial clefts are the most frequent craniofacial defects, which affect 1.5 in 1,000 newborns worldwide. Orofacial clefting is caused by abnormal facial development. In human and mouse, initial growth and patterning of the face relies on several small buds of tissue, the facial prominences. The face is derived from six main prominences: paired frontal nasal processes (FNP), maxillary prominences (MxP) and mandibular prominences (MdP). These prominences consist of swellings of mesenchyme that are encased in an overlying epithelium. Studies in multiple species have shown that signaling crosstalk between facial ectoderm and mesenchyme is critical for shaping the face. Yet, mechanistic details concerning the genes involved in these signaling relays are lacking. One way to gain a comprehensive understanding of gene expression, transcription factor binding, and chromatin marks associated with the developing facial ectoderm and mesenchyme is to isolate and characterize the separated tissue compartments. Here we present a method for separating facial ectoderm and mesenchyme at embryonic day (E) 10.5, a critical developmental stage in mouse facial formation that precedes fusion of the prominences. Our method is adapted from the approach we have previously used for dissecting facial prominences. In this earlier study we had employed inbred C57BL/6 mice as this strain has become a standard for genetics, genomics and facial morphology. Here, though, due to the more limited quantities of tissue available, we have utilized the outbred CD-1 strain that is cheaper to purchase, more robust for husbandry, and tending to produce more embryos (12-18) per litter than any inbred mouse strain. Following embryo isolation, neutral protease Dispase II was used to treat the whole embryo. Then, the facial prominences were dissected out, and the facial ectoderm was separated from the mesenchyme. This method keeps both the facial ectoderm and mesenchyme intact. The samples obtained using this methodology can be used for techniques including protein detection, chromatin immunoprecipitation (ChIP) assay, microarray studies, and RNA-seq.
Topics: Animals; Dissection; Ectoderm; Embryo, Mammalian; Face; Female; Mesoderm; Mice; Mice, Inbred C57BL; Pregnancy
PubMed: 23603693
DOI: 10.3791/50248