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
Source: PubMed


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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    • "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 [49]. Indeed, we observed that ependymal cells disappeared in the afadin-cKO mice, as shown in the hyh mutant mice [31]. "
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    ABSTRACT: Adherens junctions (AJs) play a role in mechanically connecting adjacent cells to maintain tissue structure, particularly in epithelial cells. The major cell-cell adhesion molecules at AJs are cadherins and nectins. Afadin binds to both nectins and α-catenin and recruits the cadherin-β-catenin complex to the nectin-based cell-cell adhesion site to form AJs. To explore the role of afadin in radial glial and ependymal cells in the brain, we generated mice carrying a nestin-Cre-mediated conditional knockout (cKO) of the afadin gene. Newborn afadin-cKO mice developed hydrocephalus and died neonatally. The afadin-cKO brain displayed enlarged lateral ventricles and cerebral aqueduct, resulting from stenosis of the caudal end of the cerebral aqueduct and obliteration of the ventral part of the third ventricle. Afadin deficiency further caused the loss of ependymal cells from the ventricular and aqueductal surfaces. During development, radial glial cells, which terminally differentiate into ependymal cells, scattered from the ventricular zone and were replaced by neurons that eventually covered the ventricular and aqueductal surfaces of the afadin-cKO midbrain. Moreover, the denuded ependymal cells were only occasionally observed in the third ventricle and the cerebral aqueduct of the afadin-cKO midbrain. Afadin was co-localized with nectin-1 and N-cadherin at AJs of radial glial and ependymal cells in the control midbrain, but these proteins were not concentrated at AJs in the afadin-cKO midbrain. Thus, the defects in the afadin-cKO midbrain most likely resulted from the destruction of AJs, because AJs in the midbrain were already established before afadin was genetically deleted. These results indicate that afadin is essential for the maintenance of AJs in radial glial and ependymal cells in the midbrain and is required for normal morphogenesis of the cerebral aqueduct and ventral third ventricle in the midbrain.
    PLoS ONE 11/2013; 8(11):e80356. DOI:10.1371/journal.pone.0080356 · 3.23 Impact Factor
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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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    ABSTRACT: Epithelial tubes are the infrastructure for organs and tissues, and tube morphogenesis requires precise orchestration of cell signaling, shape, migration, and adhesion. Follicle cells in the Drosophila ovary form a pair of epithelial tubes whose lumens act as molds for the eggshell respiratory filaments, or dorsal appendages (DAs). DA formation is a robust and accessible model for studying the patterning, formation, and expansion of epithelial tubes. Tramtrack69 (TTK69), a transcription factor that exhibits a variable embryonic DNA-binding preference, controls DA lumen volume and shape by promoting tube expansion; the tramtrack mutation twin peaks (ttk(twk)) reduces TTK69 levels late in oogenesis, inhibiting this expansion. Microarray analysis of wild type and ttk(twk) ovaries, followed by in situ hybridization and RNAi of candidate genes, identified the Phospholipase B-like protein Lamina ancestor (LAMA), the scaffold protein Paxillin, the endocytotic regulator Shibire (Dynamin), and the homeodomain transcription factor Mirror, as TTK69 effectors of DA-tube expansion. These genes displayed enriched expression in DA-tube cells, except lama, which was expressed in all follicle cells. All four genes showed reduced expression in ttk(twk) mutants and exhibited RNAi phenotypes that were enhanced in a ttk(twk)/+ background, indicating ttk(twk) genetic interactions. Although previous studies show that Mirror patterns the follicular epithelium prior to DA tubulogenesis, we show that Mirror has an independent, novel role in tube expansion, involving positive regulation of Paxillin. Thus, characterization of ttk(twk)-differentially expressed genes expands the network of TTK69 effectors, identifies novel epithelial tube-expansion regulators, and significantly advances our understanding of this vital developmental process.
    Developmental Biology 03/2013; 378(2). DOI:10.1016/j.ydbio.2013.03.017 · 3.55 Impact Factor
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