Mural cells (MCs) are essential for blood vessel stability and function; however, the mechanisms that regulate MC development remain incompletely understood, in particular those involved in MC specification. Here, we investigated the first steps of MC formation in zebrafish using transgenic reporters. Using and reporters, we show that the onset of expression of , a pericyte marker in adult mice and zebrafish, occurs almost coincidentally with an increment in expression in peri-arterial mesenchymal cells, suggesting that these transcriptional changes mark the specification of MC lineage cells from naïve mesenchymal cells. The emergence of peri-arterial MCs required Notch signaling. We found that -positive cells express in addition to , and although depletion of or failed to block MC emergence, embryos depleted of both and lost mesoderm- as well as neural crest-derived MCs. Using reporters that read out Notch signaling and Notch2 receptor cleavage, we show that Notch activation in the mesenchyme precedes specification into MCs. Taken together, these results show that Notch signaling is necessary for peri-arterial MC specification.
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http://dx.doi.org/10.1242/dev.165589 | DOI Listing |
Naturwissenschaften
January 2025
Institute of Bioengineering and Biosciences, School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
While most dentate non-mammalian vertebrates possess simple conical teeth, some demonstrate complex tooth shapes. Lake Malawi cichlid fishes are an extreme example of this, exhibiting a myriad of tooth shapes driven by an ecologically derived rapid evolution of closely related but distinct species. Tooth shape in mammals is generally considered to be established by signaling centers called primary and secondary enamel knots, which are not believed to be present in non-mammalian vertebrates.
View Article and Find Full Text PDFBackground: Metastasis is the leading cause of breast cancer (BC) death, and tumor cells must migrate and invade to metastasize. BC cells that express the pro-metastatic actin regulatory protein MenaINV have an enhanced ability to migrate and intravasate within the primary tumor and extravasate at secondary sites. Though chemotherapy improves patient survival, treatment with paclitaxel leads to upregulation of MenaINV and an increase in metastasis in mice.
View Article and Find Full Text PDFThe TEAD family of transcription factors are best known as the DNA-binding factor in the Hippo pathway, where they act by interacting with transcriptional coactivators YAP and TAZ (YAP/TAZ). Despite the importance of the Hippo pathway, the in vivo functions of TEAD in mammals have not been well established. By comparing mouse mutants lacking TEAD1 and TEAD2 (TEAD1/2) to those lacking YAP/TAZ, we found that TEAD1/2 have both YAP/TAZ-dependent and -independent functions during ventral telencephalon development.
View Article and Find Full Text PDFLife Sci
January 2025
TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China. Electronic address:
Aims: Vertebrates vary greatly in their abilities to regenerate injured hearts. Zebrafish possess a remarkable capacity for cardiac regeneration, making them an excellent model for regeneration research. Recent studies have reported the activation and underlying regulatory mechanisms of leptin b (lepb) and the leptin b-linked enhancer (LEN) in injured hearts.
View Article and Find Full Text PDFJ Biol Chem
January 2025
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8; Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON, Canada, M5G 2M9. Electronic address:
The NUMB gene encodes a conserved adaptor protein with roles in asymmetric cell division and cell fate determination. First described as an inhibitor of Notch signaling, multi-functional NUMB proteins regulate multiple cellular pathways through protein complexes with ubiquitin ligases, polarity proteins and the endocytic machinery. The vertebrate NUMB protein isoforms were identified over two decades ago, yet the majority of functional studies exploring NUMB function in endocytosis, cell migration and adhesion, development and disease have largely neglected the potential for distinct isoform activity in design and interpretation.
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