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The Journal of Clinical Investigation Sep 2021Hypoxia-induced pulmonary hypertension (PH) is one of the most common and deadliest forms of PH. Fibroblast growth factor receptors 1 and 2 (FGFR1/2) are elevated in...
Hypoxia-induced pulmonary hypertension (PH) is one of the most common and deadliest forms of PH. Fibroblast growth factor receptors 1 and 2 (FGFR1/2) are elevated in patients with PH and in mice exposed to chronic hypoxia. Endothelial FGFR1/2 signaling is important for the adaptive response to several injury types and we hypothesized that endothelial FGFR1/2 signaling would protect against hypoxia-induced PH. Mice lacking endothelial FGFR1/2, mice with activated endothelial FGFR signaling, and human pulmonary artery endothelial cells (HPAECs) were challenged with hypoxia. We assessed the effect of FGFR activation and inhibition on right ventricular pressure, vascular remodeling, and endothelial-mesenchymal transition (EndMT), a known pathologic change seen in patients with PH. Hypoxia-exposed mice lacking endothelial FGFRs developed increased PH, while mice overexpressing a constitutively active FGFR in endothelial cells did not develop PH. Mechanistically, lack of endothelial FGFRs or inhibition of FGFRs in HPAECs led to increased TGF-β signaling and increased EndMT in response to hypoxia. These phenotypes were reversed in mice with activated endothelial FGFR signaling, suggesting that FGFR signaling inhibits TGF-β pathway-mediated EndMT during chronic hypoxia. Consistent with these observations, lung tissue from patients with PH showed activation of FGFR and TGF-β signaling. Collectively, these data suggest that activation of endothelial FGFR signaling could be therapeutic for hypoxia-induced PH.
Topics: Animals; Endothelium; Female; Fibroblast Growth Factors; Humans; Hypertension, Pulmonary; Hypoxia; Male; Mesoderm; Mice; Mice, Knockout; Receptors, Fibroblast Growth Factor; Signal Transduction; Vascular Remodeling
PubMed: 34623323
DOI: 10.1172/JCI141467 -
Journal of Morphology Feb 2022Parrot embryos carry peculiar appendages at their developing beak that have been described as pseudoteeth. To better characterize the pattern of development responsible...
Parrot embryos carry peculiar appendages at their developing beak that have been described as pseudoteeth. To better characterize the pattern of development responsible for the emergence of these dental appendages, we examined parrot embryos combining conventional histology and microtomography approaches. Using immunohistochemistry, we observed the epithelial and mesenchymal expression of several proteins involved in tooth development in mammals. Parrot pseudoteeth arose by epithelial and mesenchymal evagination, and their early development was similar to the ontogeny of scales and feathers. There was no enamel tissue, and the evaginations were surrounded by the rhamphotheca. In adults, the rhamphotheca covers entirely the appendages, now represented by bone evaginations, which were more numerous in the lower than in the upper beak, being similar to the osseous teeth of the fossil Pelagornithidae. These embryonic pseudoteeth resembled reptile's first-generation teeth and dental appendages of chicken talpid mutants. Proteins involved in mammalian odontogenesis, such as SHH, BMP4, PITX2, and PAX9, were found to be generally expressed in beak epithelium and mesenchyme during parrot pseudoteeth development, with clusters of high-level expression in the pseudoteeth rudiments. This suggests that a similar, highly conserved gene expression program gives rise to the appearance of odontode derivatives in numerous species, despite their divergent developmental paths. These results provide new insights into the development and evolution of odontode-derived structures in vertebrates.
Topics: Animals; Beak; Fossils; Gene Expression Regulation, Developmental; Mesoderm; Odontogenesis; Parrots; Tooth
PubMed: 34910319
DOI: 10.1002/jmor.21437 -
Experimental Cell Research Jan 2022Drosophila embryonic somatic muscles represent a simple and tractable model system to study the gene regulatory networks that control diversification of cell types.... (Review)
Review
Drosophila embryonic somatic muscles represent a simple and tractable model system to study the gene regulatory networks that control diversification of cell types. Somatic myogenesis in Drosophila is initiated by intrinsic action of the mesodermal master gene twist, which activates a cascade of transcriptional outputs including myogenic differentiation factor Mef2, which triggers all aspects of the myogenic differentiation program. In parallel, the expression of a combinatorial code of identity transcription factors (iTFs) defines discrete particular features of each muscle fiber, such as number of fusion events, and specific attachment to tendon cells or innervation, thus ensuring diversification of muscle types. Here, we take the example of a subset of lateral transverse (LT) muscles and discuss how the iTF code and downstream effector genes progressively define individual LT properties such as fusion program, attachment and innervation. We discuss new challenges in the field including the contribution of posttranscriptional and epitranscriptomic regulation of gene expression in the diversification of cell types.
Topics: Animals; Cell Differentiation; Drosophila Proteins; Drosophila melanogaster; Embryo, Nonmammalian; Embryonic Development; Gene Expression Regulation, Developmental; Mesoderm; Muscle Development; Muscles; Myogenic Regulatory Factors
PubMed: 34838813
DOI: 10.1016/j.yexcr.2021.112950 -
Monographs in Clinical Cytology 2020This chapter describes the mesenchymal tumors of the pancreas which are of rare occurrence. Mesenchymal tumors of the pancreas may be benign, of intermediate biological... (Review)
Review
This chapter describes the mesenchymal tumors of the pancreas which are of rare occurrence. Mesenchymal tumors of the pancreas may be benign, of intermediate biological potential or malignant. The more commonly occurring mesenchymal tumors of the pancreas are described in this chapter along with their appropriate immunohistochemical workup and differential diagnoses.
Topics: Diagnosis, Differential; Humans; Mesoderm; Neoplasms; Pancreas; Pancreatic Neoplasms
PubMed: 32987394
DOI: 10.1159/000455739 -
Current Topics in Developmental Biology 2021Branching morphogenesis generates epithelial trees which facilitate gas exchange, filtering, as well as secretion processes with their large surface to volume ratio. In... (Review)
Review
Branching morphogenesis generates epithelial trees which facilitate gas exchange, filtering, as well as secretion processes with their large surface to volume ratio. In this review, we focus on the developmental mechanisms that control the early stages of lung branching morphogenesis. Lung branching morphogenesis involves the stereotypic, recurrent definition of new branch points, subsequent epithelial budding, and lung tube elongation. We discuss current models and experimental evidence for each of these steps. Finally, we discuss the role of the mesenchyme in determining the organ-specific shape.
Topics: Cell Division; Lung; Mesoderm; Morphogenesis; Organogenesis
PubMed: 33820622
DOI: 10.1016/bs.ctdb.2021.02.002 -
Seminars in Cell & Developmental Biology Aug 2019The pancreas is a compound gland comprised of both exocrine acinar and duct cells as well as endocrine islet cells. Most notable amongst the latter are the... (Review)
Review
The pancreas is a compound gland comprised of both exocrine acinar and duct cells as well as endocrine islet cells. Most notable amongst the latter are the insulin-synthesizing β-cells, loss or dysfunction of which manifests in diabetes mellitus. All exocrine and endocrine cells derive from multipotent pancreatic progenitor cells arising from the primitive gut epithelium via inductive interactions with adjacent mesodermal tissues. Research in the last two decades has revealed the identity of many of these extrinsic cues and they include signaling molecules used in many other developmental contexts such as retinoic acid, fibroblast growth factors, and members of the TGF-β superfamily. As important as these inductive cues is the absence of other signaling molecules such as hedgehog family members. Much has been learned about the interactions of extrinsic factors with fate regulators intrinsic to the pancreatic endoderm. This new knowledge has had tremendous impact on the development of directed differentiation protocols for converting pluripotent stem cells to β-cells in vitro.
Topics: Animals; Humans; Mesoderm; Mice; Pancreas
PubMed: 30142440
DOI: 10.1016/j.semcdb.2018.08.008 -
Developmental Biology Jul 2020Initial limb chondrogenesis offers the first differentiated tissues that resemble the mature skeletal anatomy. It is a developmental progression of three tissues. The... (Review)
Review
Initial limb chondrogenesis offers the first differentiated tissues that resemble the mature skeletal anatomy. It is a developmental progression of three tissues. The limb begins with undifferentiated mesenchyme-1, some of which differentiates into condensations-2, and this tissue then transforms into cartilage-3. Each tissue is identified by physical characteristics of cell density, shape, and extracellular matrix composition. Tissue specific regimes of gene regulation underlie the diagnostic physical and chemical properties of these three tissues. These three tissue based regimes co-exist amid a background of other gene regulatory regimes within the same tissues and time-frame of limb development. The bio-molecular indicators of gene regulation reveal six identifiable patterns. Three of these patterns describe the unique bio-molecular indicators of each of the three tissues. A fourth pattern shares bio-molecular indicators between condensation and cartilage. Finally, a fifth pattern is composed of bio-molecular indicators that are found in undifferentiated mesenchyme prior to any condensation differentiation, then these bio-molecular indicators are upregulated in condensations and downregulated in undifferentiated mesenchyme. The undifferentiated mesenchyme that remains in between the condensations and cartilage, the interdigit, contains a unique set of bio-molecular indicators that exhibit dynamic behaviour during chondrogenesis and therefore argue for its own inclusion as a tissue in its own right and for more study into this process of differentiation.
Topics: Animals; Cartilage; Cell Differentiation; Chondrogenesis; Extracellular Matrix; Gene Expression Regulation, Developmental; Limb Buds; Mesoderm; Proteoglycans
PubMed: 32417169
DOI: 10.1016/j.ydbio.2020.04.009 -
Seminars in Cell & Developmental Biology Jul 2022A critical stage in the development of all vertebrate embryos is the generation of the body plan and its subsequent patterning and regionalisation along the main... (Review)
Review
A critical stage in the development of all vertebrate embryos is the generation of the body plan and its subsequent patterning and regionalisation along the main anterior-posterior axis. This includes the formation of the vertebral axial skeleton. Its organisation begins during early embryonic development with the periodic formation of paired blocks of mesoderm tissue called somites. Here, we review axial patterning of somites, with a focus on studies using amniote model systems - avian and mouse. We summarise the molecular and cellular mechanisms that generate paraxial mesoderm and review how the different anatomical regions of the vertebral column acquire their specific identity and thus shape the body plan. We also discuss the generation of organoids and embryo-like structures from embryonic stem cells, which provide insights regarding axis formation and promise to be useful for disease modelling.
Topics: Animals; Body Patterning; Embryonic Development; Gene Expression Regulation, Developmental; Mesoderm; Mice; Somites; Spine; Vertebrates
PubMed: 34690064
DOI: 10.1016/j.semcdb.2021.10.003 -
Methods in Molecular Biology (Clifton,... 2021As our understanding of Epithelial Mesenchymal Transition (EMT) increases, the original binary concept of E versus M no longer fits with experimental evidence....
As our understanding of Epithelial Mesenchymal Transition (EMT) increases, the original binary concept of E versus M no longer fits with experimental evidence. Re-definition of the EMT paradigm as spectral transitions between a full epithelium and a full mesenchyme suggests the existence of a virtual infinity of intermediate cellular states. The new challenge is to develop technical tools needed to contextualize each of these states and identify biologically significant cellular mechanisms that could be targeted in combatting EMT-related diseases.
Topics: Cell Culture Techniques; Epithelial-Mesenchymal Transition; Epithelium; Humans; Mesoderm
PubMed: 32939711
DOI: 10.1007/978-1-0716-0779-4_5 -
Seminars in Cell & Developmental Biology Aug 2019The liver is an indispensable organ for metabolism and drug detoxification. The liver consists of endoderm-derived hepatobiliary lineages and various mesoderm-derived... (Review)
Review
The liver is an indispensable organ for metabolism and drug detoxification. The liver consists of endoderm-derived hepatobiliary lineages and various mesoderm-derived cells, and interacts with the surrounding tissues and organs through the ventral mesentery. Liver development, from hepatic specification to liver maturation, requires close interactions with mesoderm-derived cells, such as mesothelial cells, hepatic stellate cells, mesenchymal cells, liver sinusoidal endothelial cells and hematopoietic cells. These cells affect liver development through precise signaling events and even direct physical contact. Through the use of new techniques, emerging studies have recently led to a deeper understanding of liver development and its related mechanisms, especially the roles of mesodermal cells in liver development. Based on these developments, the current protocols for in vitro hepatocyte-like cell induction and liver-like tissue construction have been optimized and are of great importance for the treatment of liver diseases. Here, we review the roles of mesoderm-derived cells in the processes of liver development, hepatocyte-like cell induction and liver-like tissue construction.
Topics: Animals; Humans; Liver; Mesoderm; Mice
PubMed: 30193996
DOI: 10.1016/j.semcdb.2018.09.003