Mechanisms of tissue fusion during development
HHMI, Department of Pediatrics, Cell Biology Stem Cells and Development Graduate Program, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO 80045, USA.Development (Impact Factor: 6.46). 05/2012; 139(10):1701-11. DOI: 10.1242/dev.068338
Tissue fusion events during embryonic development are crucial for the correct formation and function of many organs and tissues, including the heart, neural tube, eyes, face and body wall. During tissue fusion, two opposing tissue components approach one another and integrate to form a continuous tissue; disruption of this process leads to a variety of human birth defects. Genetic studies, together with recent advances in the ability to culture developing tissues, have greatly enriched our knowledge of the mechanisms involved in tissue fusion. This review aims to bring together what is currently known about tissue fusion in several developing mammalian organs and highlights some of the questions that remain to be addressed.
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- "Tubular morphogenesis (tubulogenesis) is essential for normal embryonic development, and organs that undergo tubulogenesis are frequently affected by congenital anomalies (Ray and Niswander, 2012). A variety of mechanisms can drive tube formation, such as the wrapping mechanism of neurulation, budding of the salivary and mammary glands, and the delamination/migration process of bile duct development (Andrew and Ewald, 2010; Caviglia and Luschnig, 2014; Luschnig and Uv, 2014; Zegers, 2014). "
ABSTRACT: Congenital anomalies frequently occur in organs that undergo tubulogenesis. Hypospadias is a urethral tube defect defined by mislocalized, oversized, or multiple openings of the penile urethra. Deletion of Fgfr2 or its ligand Fgf10 results in severe hypospadias in mice, in which the entire urethral plate is open along the ventral side of the penis. In the genital tubercle, the embryonic precursor of the penis and clitoris, Fgfr2 is expressed in two epithelial populations: the endodermally derived urethral epithelium and the ectodermally derived surface epithelium. Here, we investigate the tissue-specific roles of Fgfr2 in external genital development by generating conditional deletions of Fgfr2 in each of these cell types. Conditional deletion of Fgfr2 results in two distinct phenotypes: endodermal Fgfr2 deletion causes mild hypospadias and inhibits maturation of a complex urethral epithelium, whereas loss of ectodermal Fgfr2 results in severe hypospadias and absence of the ventral prepuce. Although these cell type-specific mutants exhibit distinctive genital anomalies, cellular analysis reveals that Fgfr2 regulates epithelial maturation and cell cycle progression in the urethral endoderm and in the surface ectoderm. The unexpected finding that ectodermal deletion of Fgfr2 results in the most severe hypospadias highlights a major role for Fgfr2 in the developing genital surface epithelium, where epithelial maturation is required for maintenance of a closed urethral tube. These results demonstrate that urethral tubulogenesis, prepuce morphogenesis, and sexually dimorphic patterning of the lower urethra are controlled by discrete regions of Fgfr2 activity. © 2015. Published by The Company of Biologists Ltd.
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- "When the fusion occurs, tissues proliferate and position themselves at a place close enough to fuse. Then, the epithelial cells of the apical luminal surface finally disappear or lose their epithelial features in various mechanisms, such as apoptosis, epithelial-mesenchymal transition, cell migration, denudation, or combinations of these mechanisms, depending on the organs . Indeed, we observed that ependymal cells disappeared in the afadin-cKO mice, as shown in the hyh mutant mice . "
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- "Epithelial tubes are essential structures in metazoan organs and tissues and thus, errors during tube morphogenesis can have profound developmental consequences. Failure of gastrulation will arrest development and defects in neural tube closure may result in spina bifida or anencephaly (Botto et al., 1999; Davidoff et al., 2002; Wallingford, 2005; Ray and Niswander, 2012). Gaining insight into the molecular and cellular requirements of tubulogenesis will augment our understanding of this developmental process and illuminate underlying causes of developmental tube defects, leading to better diagnostics and treatments. "
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