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Background: The vertebrate enteric nervous system (ENS) consists of a series of interconnected ganglia within the gastrointestinal (GI) tract, formed during development following migration of enteric neural crest cells (ENCCs) into the primitive gut tube. Much work has been done to unravel the complex nature of extrinsic and intrinsic factors that regulate processes that direct migration, proliferation, and differentiation of ENCCs. However, ENS development is a complex process, and we still have much to learn regarding the signaling factors that regulate ENCC development.
Results: Here in zebrafish, through transcriptomic, in situ transcript expression, immunohistochemical analysis, and chemical attenuation, we identified a time-dependent role for bone morphogenetic protein (BMP) in the maintenance of Phox2bb enteric progenitor numbers and/or time of differentiation of the progenitor pool. In support of our in silico transcriptomic analysis, we identified expression of a novel ENS ligand-encoding transcript, bmp5, within developmental regions of ENCCs. Through generation of a novel mutant bmp5 and bmp5 crispants, we identified a functional role for BMP5 in proper GI tract colonization, whereby phox2bb enteric progenitor numbers were reduced.
Conclusion: Altogether, this work identified time-dependent roles for BMP signaling and a novel extrinsic factor, BMP5, that is necessary for vertebrate ENS formation.
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http://dx.doi.org/10.1002/dvdy.737 | DOI Listing |
Pulm Circ
July 2025
Division of Pulmonary, Critical Care, and Sleep Medicine Tufts Medical Center Boston Massachusetts USA.
Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, proliferation, fibrosis, and microthrombosis of the pulmonary vasculature, which causes elevated pulmonary arterial pressure and vascular resistance leading to right ventricular failure and death. Previous treatments targeted three known pathways involved in the development of PAH: endothelin, nitric oxide, and prostacyclin. Dysfunctional signaling of the transforming growth factor-beta (TGF-β) family, via bone morphogenetic protein (BMP) receptor 2 and activin signaling, has also been implicated in PAH leading to the development of a new class of therapies.
View Article and Find Full Text PDFComp Biochem Physiol C Toxicol Pharmacol
September 2025
Department of Biological Sciences, Clemson University, Clemson, SC, USA; Clemson University Center for Human Genetics, Greenwood, SC, USA. Electronic address:
Tetrabromobisphenol A (TBBPA), a widely used flame retardant in textiles and electronics, poses toxicological risks through both environmental and indoor exposures. Biomonitoring studies have detected significant TBBPA levels in prenatal environments, including cord blood, raising concerns about developmental impacts. Using zebrafish as a model, this study addresses critical gaps in understanding how developmental TBBPA exposures perturb regulatory pathways that govern dorsoventral patterning.
View Article and Find Full Text PDFJ Proteome Res
September 2025
State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
Shell matrix proteins (SMPs) are fundamental biological macromolecules for mollusk shell formation, yet fewer than 400 SMPs in mollusks have been previously identified, hindering our understanding of how mollusks construct and maintain their shells. Here, we identified 1689 SMPs in the Pacific oyster using three different mass spectrometry techniques, representing a significant methodological advancement in shell proteomics, enabling a 6.52-fold increase in SMP identification compared to previous studies.
View Article and Find Full Text PDFDev Biol
September 2025
Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115 USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115 USA; Harvard Stem Cell Institute, 7 Divinity Ave, Cambridge, MA 02138 USA. Electronic address:
The mechanisms mediating endochondral bone formation remain incompletely understood. Here, we show that CXXC Finger Protein 1 (CFP1) is required for the onset of chondrogenesis during forelimb development. CFP1-deficient mesenchymal progenitor cells (LMPs) retain an immature molecular signature with elevated FGF and SHH signaling and repressed BMP signaling, in part, due to (1) reduced expression of type I BMP receptors, (2) reduced Smad1 protein levels and (3) an altered extracellular niche.
View Article and Find Full Text PDFAm J Hematol
September 2025
Nephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
The bone morphogenetic protein (BMP)-SMAD signaling pathway is central to regulating hepcidin, the master regulator of systemic iron homeostasis. We have previously demonstrated that BMP6, BMP2, and, to a lesser extent, BMP5 are the major ligands contributing to hepcidin and iron homeostasis regulation in vivo. Hemojuvelin (HJV) and homeostatic iron regulator (HFE) are hepcidin modulators that are mutated in hereditary hemochromatosis.
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