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The formation of a complex multicellular organism from a single cell is one of the most amazing processes of biology. Embryonic development is characterised by the careful regulation of cellular behaviours such that cells proliferate, migrate, differentiate and form tissues at the correct place and time. These processes are genetically controlled and depend both on the history of cells, their lineage, and on the activities of signalling pathways, which coordinate the cell interactions leading to organogenesis. The aim of the Frontiers research topic “Signalling pathways in embryonic development” has been to provide a forum for experts in cell and developmental biology to share recent advances in the field of signalling during embryonic development. Sixteen articles in a variety of formats are united in this Topic, offering a valuable collection for researchers looking for an update in the knowledge of signalling pathways operating during embryogenesis. The works, focused mainly on vertebrates, explore different aspects of this theme from cell communication to organ formation and have implications for areas as distant as evolution or pathology. Understanding developmental signalling pathways is important for several reasons. It gives us information about basic mechanisms of cell function and interactions needed for morphogenesis and organogenesis. It uncovers the basis of congenital malformations, since errors at any step of cell signalling during development are a major cause of defects. This fundamental insight gives us clues to understand the mechanisms operating in evolution that explain diversity in form and function. And finally, it allows the identification of possible causes of disease in the adult organism (such as cancer or degenerative diseases) pinpointing possible targets for therapeutic approaches.

development --- Shh --- Fgf --- Notch --- embryo --- Signalling --- organogenesis --- Wnt

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The formation of a complex multicellular organism from a single cell is one of the most amazing processes of biology. Embryonic development is characterised by the careful regulation of cellular behaviours such that cells proliferate, migrate, differentiate and form tissues at the correct place and time. These processes are genetically controlled and depend both on the history of cells, their lineage, and on the activities of signalling pathways, which coordinate the cell interactions leading to organogenesis. The aim of the Frontiers research topic “Signalling pathways in embryonic development” has been to provide a forum for experts in cell and developmental biology to share recent advances in the field of signalling during embryonic development. Sixteen articles in a variety of formats are united in this Topic, offering a valuable collection for researchers looking for an update in the knowledge of signalling pathways operating during embryogenesis. The works, focused mainly on vertebrates, explore different aspects of this theme from cell communication to organ formation and have implications for areas as distant as evolution or pathology. Understanding developmental signalling pathways is important for several reasons. It gives us information about basic mechanisms of cell function and interactions needed for morphogenesis and organogenesis. It uncovers the basis of congenital malformations, since errors at any step of cell signalling during development are a major cause of defects. This fundamental insight gives us clues to understand the mechanisms operating in evolution that explain diversity in form and function. And finally, it allows the identification of possible causes of disease in the adult organism (such as cancer or degenerative diseases) pinpointing possible targets for therapeutic approaches.

development --- Shh --- Fgf --- Notch --- embryo --- Signalling --- organogenesis --- Wnt

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Neuronal function relies on the establishment of proper connections between neurons and their target cells during development. This basic statement involves several cellular processes, such as neuronal differentiation, the polarized outgrowth of axons and dendrites from differentiated neurons, and the pathfinding of axons towards target cells. The subsequent recognition of complementary synaptic partners finally triggers the formation, maturation, and maintenance of functional synapses. Morphogens are secreted signaling molecules commanding tissue patterning and cell identity during early embryonic development. Remarkably, growing evidence over the last years arising from different invertebrate and vertebrate model organisms has shown that, after cell fate has been established, morphogens also control the precise wiring and function in the developing and mature nervous system. Accordingly, dysfunctions of the signaling pathways activated by these molecules contribute to synaptic disassembly and altered function in diseases affecting the nervous system. We consider it timely to bring together cumulative evidence pointing to crucial roles for signaling activated by different morphogens in the establishment of precise contacts between neurons and their synaptic partners. Therefore, this research topic issue combines review and research articles aimed to cover the functional relevance of such morphogens on the different steps involved in synaptic assembly and function. Diverse model systems of physiological or pathological conditions have been included, as well as different cellular, biochemical and molecular approaches. Altogether, they contribute in different and complementary ways to build a holistic view of the roles that early development morphogens play during the assembly, maintenance and/or regeneration of functional synapses.

Shh --- Nervous System --- BMP --- neurodegeneration --- synapse --- Wnt --- Morphogens --- Neurogenesis --- Shh --- Nervous System --- BMP --- neurodegeneration --- synapse --- Wnt --- Morphogens --- Neurogenesis

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The Hedgehog signaling pathway is an evolutionarily conserved pathway that governs complex developmental processes, including stem cell maintenance, proliferation, differentiation, and patterning. Several recent studies have shown that the aberrant activation of Hedgehog signaling is associated with neoplastic transformation, cancer cell proliferation, metastasis, multiple cancers’ drug resistance, and survival rates. This book focuses on several aspects of Hedgehog signaling in organogenesis and the tumor microenvironment, and presents reviews and original papers on recent efforts in the field of Hedgehog signaling.

Cyp26 enzymes --- congenital anomalies --- CRE/LoxP --- hedgehog signaling --- mouse models --- retinoic acid --- smoothened --- sonic hedgehog --- sonic hedgehog (SHH) --- oral squamous cell carcinoma (OSCC) --- tumor microenvironment (TME) --- tumor-associated macrophages (TAMs) --- cancer-associated fibroblasts (CAFs) --- tumor-associated angiogenesis --- hedgehog --- growth plate --- endochondral ossification --- chondrocyte --- osteoblast --- bone disease --- TMJ --- synovial joint --- articular disc --- Ihh --- PTHrP --- osteoarthritis --- epithelial–mesenchymal interaction (EMI) --- prostate cancer --- external genitalia --- androgen --- basement membrane --- bone morphogenetic protein --- stem cell --- animal experiment --- fracture healing --- cancer stem cells --- hypospadias --- urethra --- penis --- bone --- hedgehog signalling --- tooth development --- epithelial and mesenchymal interaction --- Gli1 --- mesenchymal stem cell --- lineage tracing analysis --- stem cell marker --- n/a --- epithelial-mesenchymal interaction (EMI)

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Plant alkaloids are critical components of modern medicine and pharmaceuticals. These compounds are also becoming increasingly important for industrial uses as part of the green chemistry revolution. This Special Issue will focus on the molecular advances being made in understanding how such a large and diverse class of compounds are made by plants and how metabolic engineering advances are increasing the overall yield of crucial precursors.

Research & information: general --- Biology, life sciences --- canthin-6-one --- Picrolemma huberi --- Simaroubaceae --- antiplasmodial activity --- Sarcococca hookeriana --- sarchookloides A–C --- steroidal alkaloid --- cytotoxicity --- Rhodophiala --- alkaloids --- molecular docking --- AChE --- BuChE --- GC-MS --- Mahonia imbricata --- Berberidaceae --- isoquinoline alkaloid --- mahimbrine A --- hedgehog signaling --- Veratrum californicum --- cyclopamine --- HPLC-MS --- Shh-Light II cells --- halogencyclopropane --- dichlorocarbene --- epoxidation --- vindoline --- catharanthine --- dimer alkaloids --- vindoline trimer --- Ruta graveolens --- photosystem II --- Chl a fluorescence --- Hill reaction inhibitors --- acridone alkaloids --- benzylisoquinoline alkaloids --- cytochrome P450 monooxygenase --- medicinal properties --- methyltransferase --- Nelumbo nucifera --- norcoclaurine synthase --- sacred lotus --- stereochemistry --- Aristotelia chilensis Molina Stuntz --- vascular activity --- endothelium-independent --- indole alkaloid --- 8-oxo-9-dihydromakomakine --- voltage-dependent calcium channels --- Catharanthus roseus --- cambial meristematic cells --- Aspergillus flavus --- terpenoid indole alkaloids --- biosynthesis --- Buxaceae --- Borago officinalis --- Crassocephalum --- Copper-dependent diamine oxidase --- Gynura bicolor --- Homospermidine synthase --- Lolium perenne --- Necic acids --- Necine bases --- Pyrrolizidine alkaloid biosynthesis --- Senecionine --- tropane alkaloids --- scopolamine --- cocaine --- calystegine --- chemistry --- pharmacology --- biotechnological production --- Erythroxylaceae --- Erythroxylum coca --- next generation sequencing --- traditional medicine --- bioprospecting --- tropane --- late-stage functionalization --- sulfinate --- DiversinateTM --- natural product --- medicinal chemistry --- papaverine --- scaffold --- library --- biodiscovery --- Swinglea glutinosa --- dereplication --- acridones --- phenylacrylamides --- canthin-6-one --- Picrolemma huberi --- Simaroubaceae --- antiplasmodial activity --- Sarcococca hookeriana --- sarchookloides A–C --- steroidal alkaloid --- cytotoxicity --- Rhodophiala --- alkaloids --- molecular docking --- AChE --- BuChE --- GC-MS --- Mahonia imbricata --- Berberidaceae --- isoquinoline alkaloid --- mahimbrine A --- hedgehog signaling --- Veratrum californicum --- cyclopamine --- HPLC-MS --- Shh-Light II cells --- halogencyclopropane --- dichlorocarbene --- epoxidation --- vindoline --- catharanthine --- dimer alkaloids --- vindoline trimer --- Ruta graveolens --- photosystem II --- Chl a fluorescence --- Hill reaction inhibitors --- acridone alkaloids --- benzylisoquinoline alkaloids --- cytochrome P450 monooxygenase --- medicinal properties --- methyltransferase --- Nelumbo nucifera --- norcoclaurine synthase --- sacred lotus --- stereochemistry --- Aristotelia chilensis Molina Stuntz --- vascular activity --- endothelium-independent --- indole alkaloid --- 8-oxo-9-dihydromakomakine --- voltage-dependent calcium channels --- Catharanthus roseus --- cambial meristematic cells --- Aspergillus flavus --- terpenoid indole alkaloids --- biosynthesis --- Buxaceae --- Borago officinalis --- Crassocephalum --- Copper-dependent diamine oxidase --- Gynura bicolor --- Homospermidine synthase --- Lolium perenne --- Necic acids --- Necine bases --- Pyrrolizidine alkaloid biosynthesis --- Senecionine --- tropane alkaloids --- scopolamine --- cocaine --- calystegine --- chemistry --- pharmacology --- biotechnological production --- Erythroxylaceae --- Erythroxylum coca --- next generation sequencing --- traditional medicine --- bioprospecting --- tropane --- late-stage functionalization --- sulfinate --- DiversinateTM --- natural product --- medicinal chemistry --- papaverine --- scaffold --- library --- biodiscovery --- Swinglea glutinosa --- dereplication --- acridones --- phenylacrylamides