In the mouse, Cdx1 is essential for normal anteroposterior vertebral patterning through regulation of a subset of Hox genes. Retinoic acid (RA) and certain Wnts have also been implicated in vertebral patterning, although the relationship between these signaling pathways and the regulation of mesodermal Hox gene expression is not fully understood. Prior work has shown that Cdx1 is a direct target of both Wnt and retinoid signaling pathways, and might therefore act to relay these signals to the Hox genes. Wnt and RA are believed to impact on Cdx1 through an atypical RA-response element (RARE) and Lef/Tcf-response elements (LRE), respectively, in the proximal promoter. To address the roles of these regulatory motifs and pathways, we derived mice mutated for the LRE or the LRE plus the RARE. In contrast to RARE-null mutants, which exhibit limited vertebral defects, LRE-null and LRE+RARE-null mutants exhibited vertebral malformations affecting the entire cervical region that closely phenocopied the malformations seen in Cdx1-null mutants. Mutation of the LRE also greatly reduced induction of Cdx1 by RA, demonstrating a requirement for Wnt signaling in the regulation of this gene by retinoids. LRE and LRE+RARE mutants also exhibited vertebral fusions, suggesting a defect in somitogenesis. As Wnt signaling is implicated in somitogenesis upstream of the Notch pathway, it is conceivable that Cdx1 might play a role in this process. However, none of the Notch pathway genes assessed was overtly affected.
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http://dx.doi.org/10.1242/dev.001206 | DOI Listing |
Cureus
November 2024
Department of Surgery - Center for Anatomical Science and Education, Saint Louis University School of Medicine, St. Louis, USA.
Polymicrogyria (PMG) is the most common malformation of cortical development (MCD) and presents as an irregularly patterned cortical surface with numerous small gyri and shallow sulci leading to various neurological deficits including developmental delays, intellectual disability, epilepsy, and language and motor issues. The presentation of PMG varies and is often found in conjunction with other congenital anomalies. Histologically, PMG features an abnormal cortical structure and dyslamination, resulting in its classification as a defect of neuronal migration and organization.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
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Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan 030001, China.
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View Article and Find Full Text PDFStem Cell Res Ther
December 2024
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
Background: Intrauterine adhesion (IUA), resulting from uterine trauma, is one of the major causes of female infertility. Previous studies have demonstrated that endometrial mesenchymal stem cells (eMSC) have therapeutic effects on IUA through cellular secretions. It is particularly true for most of the pre-clinical experiments performed on multiple animal models, as human-derived eMSC cannot maintain long-term engraftment in animals.
View Article and Find Full Text PDFCancer Cell Int
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Sezione di Farmacologia, Dipartimento di Medicina Interna, Università di Genova, Genova, Italy.
Background: Cellular prion protein (PrP) is a widely expressed membrane-anchored glycoprotein, which has been associated with the development and progression of several types of human malignancies, controlling cancer stem cell activity. However, the different molecular mechanisms regulated by PrP in normal and tumor cells have not been characterized yet.
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Signal Transduct Target Ther
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Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Cardiac development is a complex and intricate process involving numerous molecular signals and pathways. Researchers have explored cardiac development through a long journey, starting with early studies observing morphological changes and progressing to the exploration of molecular mechanisms using various molecular biology methods. Currently, advancements in stem cell technology and sequencing technology, such as the generation of human pluripotent stem cells and cardiac organoids, multi-omics sequencing, and artificial intelligence (AI) technology, have enabled researchers to understand the molecular mechanisms of cardiac development better.
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