Follistatin-like 1 (Fstl1) is a distantly related homolog of the Activin and Bone Morphogenetic Protein antagonist Follistatin. Interestingly, this molecule also has homology with the extracellular matrix modifying protein BM-40/SPARC/osteonectin. Previous studies in chick have identified Fstl1 as a regulator of early mesoderm patterning, somitogenesis, myogenesis and neural development. In this study, we determine the developmental expression pattern of Fstl1 during mouse development. We find that Fstl1 is ubiquitously expressed in the early embryo, and that expression becomes regionalized later during development. In the majority of tissues, Fstl1 is strongly expressed in the mesenchymal component and excluded from the epithelium. Notable exceptions include the central nervous system, in which Fstl1 expression is entirely absent with the exception of the choroid plexi and floor plate, the lung, in which Fstl1 expression can be seen in airway epithelia and the kidney, in which collecting ducts and nascent nephron epithelia express the highest levels of Fstl1.
Stimulation of the bone morphogenetic protein (BMP) pathway protects the kidney from acute and chronic injury. Numerous regulators in the kidney control BMP signaling, offering many targets for therapeutic manipulation. Here, we screened for modulators of BMP signaling in the ischemia-sensitive S3 segment and found that Chordin-like 1 is expressed in this segment of both the mouse and human nephron. Chordin-like 1 specifically antagonizes BMP7, which is expressed in the neighboring distal nephron, and this depends on the presence of the protein Twisted gastrulation. Upon ischemia-induced degeneration of the S3 segment, we observed a reduction in Chordin-like 1 expression coincident with intense BMP signaling in tubules of the recovering kidney. Restored expression accompanied proximal tubule epithelia redifferentiation, again coincident with decreased BMP signaling. We propose that Chordin-like 1 reduces BMP7 signaling in healthy proximal tubules, and the loss of this activity upon sloughing of injured epithelia promotes BMP7 signaling in repopulating, dedifferentiated epithelia. As regenerating epithelia differentiate, Chordin-like 1 is again expressed, antagonizing BMP7. These data suggest a mechanism for dynamic regulation of renoprotective BMP7 signaling in the S3 segment of the proximal tubule.
Edited by Ned ManteiThe article is dedicated to the memory of Tom Maciag, scientist, friend, and mentor.Abstract Notch signaling involves proteolytic cleavage of the transmembrane Notch receptor after binding to its transmembrane ligands, Delta or Jagged; and the resultant soluble intracellular domain of Notch stimulates a cascade of transcriptional events. The Delta1 ligand also undergoes proteolytic cleavage upon Notch binding, resulting in the production of a free intracellular domain. We demonstrate that the expression of the intracellular domain of Delta1 results in a non-proliferating senescent-like cell phenotype which is dependent on the expression of the cell cycle inhibitor, p21, and is abolished by coexpression of constitutively active Notch1. These data suggest a new intracellular role for Delta1.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.