Publications by authors named "Donna J Page"
Vascular endothelial growth factor receptors (VEGFRs) are part of the evolutionarily conserved VEGF signalling pathways that regulate the development and maintenance of the body's cardiovascular and lymphovascular systems. VEGFR3, encoded by the FLT4 gene, has an indispensable and well-characterized function in development and establishment of the lymphatic system. Autosomal dominant VEGFR3 mutations, that prevent the receptor functioning as a homodimer, cause one of the major forms of hereditary primary lymphoedema; Milroy disease.
View Article and Find Full Text PDFAngiogenesis is driven by the coordinated collective branching of specialized leading "tip" and trailing "stalk" endothelial cells (ECs). While Notch-regulated negative feedback suppresses excessive tip selection, roles for positive feedback in EC identity decisions remain unexplored. Here, by integrating computational modeling with in vivo experimentation, we reveal that positive feedback critically modulates the magnitude, timing, and robustness of angiogenic responses.
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- - Familial recurrence studies suggest a genetic link to sporadic, nonsyndromic Tetralogy of Fallot (TOF), a major type of congenital heart defect, but limited research exists on a larger scale.
- - The study analyzed 829 TOF patients through whole exome sequencing, revealing significant unique, harmful genetic variants, particularly in the NOTCH1 and FLT4 genes, which could contribute to the disease.
- - A total of 4.5% of cases had deleterious NOTCH1 variants, and further investigations indicated impaired NOTCH signaling in some variants, while FLT4 variants occurred in 2.4% of patients, highlighting potential genetic factors involved in TOF.
Article Synopsis
- Asymmetric division of stem cells creates daughter cells with different roles, influencing cell diversity in tissue formation.
- This study uses zebrafish to show that this division creates polarity, which is essential for coordinated cell movement in the formation of blood vessels (angiogenesis).
- The research demonstrates that the positioning of the mitotic spindle during cell division affects the size and signaling roles of daughter cells, impacting their formation as leader or follower cells in collective migration processes essential for development and disease.