A role for N-cadherin in mesodermal morphogenesis during gastrulation

Department of Biological Sciences, Western Michigan University, Kalamazoo, MI 49008, USA.
Developmental Biology (Impact Factor: 3.55). 11/2007; 310(2):211-25. DOI: 10.1016/j.ydbio.2007.06.023
Source: PubMed


Cell adhesion molecules mediate numerous developmental processes necessary for the segregation and organization of tissues. Here we show that the zebrafish biber (bib) mutant encodes a dominant allele at the N-cadherin locus. When knocked down with antisense oligonucleotides, bib mutants phenocopy parachute (pac) null alleles, demonstrating that bib is a gain-of-function mutation. The mutant phenotype disrupts normal cell-cell contacts throughout the mesoderm as well as the ectoderm. During gastrulation stages, cells of the mesodermal germ layer converge slowly; during segmentation stages, the borders between paraxial and axial tissues are irregular and somite borders do not form; later, myotomes are fused. During neurulation, the neural tube is disorganized. Although weaker, all traits present in bib mutants were found in pac mutants. When the distribution of N-cadherin mRNA was analyzed to distinguish mesodermal from neuroectodermal expression, we found that N-cadherin is strongly expressed in the yolk cell and hypoblast in the early gastrula, just preceding the appearance of the bib mesodermal defects. Only later is N-cadherin expressed in the anlage of the CNS, where it is found as a radial gradient in the forming neural plate. Hence, besides a well-established role in neural and somite morphogenesis, N-cadherin is essential for morphogenesis of the mesodermal germ layer during gastrulation.

9 Reads
  • Source
    • "Differentiation presumes acquisition of specific properties by cells and increase of their heterogeneity. A large number of transcripts for proteins involved in cell contacts were abundant in UFO being eliminated at SGM. Cadherins are transmembrane cell adhesion proteins that mediate various processes during development including cellular migration and tissue organization [70]. Interestingly, this study identified a large number of cadherin paralogs that are likely involved in cell sorting and tissue morphogenesis [71]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Regulation of gene expression plays a central role in embryonic development. Early stages are controlled by gametic transcripts, which are subsequently substituted with transcripts from the genome of the zygote. Transcriptomic analyses provide an efficient approach to explore the temporal gene expression profiles in embryos and to search for the developmental regulators. We report a study of early Atlantic cod development that used a genome-wide oligonucleotide microarray to examine the composition and putative roles of polyadenylated transcripts. Results The analyses were carried out in unfertilized oocytes, newly fertilized oocytes and embryos at the stages of mid-blastula transition and segmentation. Numerous genes transcribed in oocytes are involved in multiple aspects of cell maintenance and protection, including metabolism, signal perception and transduction, RNA processing, cell cycle, defense against pathogens and DNA damage. Transcripts found in unfertilized oocytes also encoded a large number of proteins implicated in cell adherence, tight junction and focal adhesion, suggesting high complexity in terms of structure and cellular interactions in embryos prior to midblastula transition (MBT). Prezygotic transcripts included multiple regulators that are most likely involved in developmental processes that take place long after fertilization, such as components of ErbB, hedgehog, notch, retinoid, TGFb, VEGF and Wnt signaling pathways, as well as transcripts involved in the development of nervous system. The major event of MBT was the activation of a large group of histones and other genes that modify chromatin structure preceding massive gene expression changes. A hallmark of events observed during segmentation was the induction of multiple transcription factors, including a large group of homeobox proteins in pace with decay of a large fraction of maternal transcripts. Microarray analyses detected a suite of master developmental regulators that control differentiation and maintenance of diverse cell lineages. Conclusions Transcriptome profiling of the early stages in Atlantic cod revealed the presence of transcripts involved in patterning and development of tissues and organs long before activation of the zygotic genome. The switch from maternal to zygotic developmental programs is associated with large-scale modification of chromosomes. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-594) contains supplementary material, which is available to authorized users.
    BMC Genomics 07/2014; 15(1):594. DOI:10.1186/1471-2164-15-594 · 3.99 Impact Factor
  • Source
    • "During embryogenesis cells undergo an epithelial-mesenchymal transition (EMT) initiating upregulation of NCad and the downregulation of ECad in the mesoderm [88]. It has been suggested that NCad expression is essential for morphogenesis of the mesodermal germ layer during gastrulation [89]. NCad expression pattern has been found complementary to that of ECad in epidermal ectoderm [88] [90] [91]. "
    Pluripotent Stem Cell Biology - Advances in Mechanisms, Methods and Models, Edited by Craig S. Atwood and Sivan Vadakkadath Meethal, 07/2014: chapter 6; InTech Europe., ISBN: 978-953-51-1590-8
  • Source
    • "Though we have shown that cdh2 mRNA overexpression is sufficient to induce fibrillogenesis and cdh2 knockdown can suppress fibronectin assembly during gastrulation, our study does not identify the cadherin whose membrane expression is increased in glypican4 mutant embryos. While Cdh2-dependent cell adhesion has been specifically linked to the directed migration of lateral mesodermal cell populations (von der Hardt et al., 2007), both Cdh1 and Cdh2 regulate zebrafish convergence and extension movements (Babb et al., 2001; Babb and Marrs, 2004; Warga and Kane, 2007) and are thus capable of influencing ECM assembly. Because we did not detect changes in total cadherin protein expression, our data suggest that trafficking of plasma membrane cadherin might be disrupted in glypican4 mutant embryos. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Zebrafish gastrulation cell movements occur in the context of dynamic changes in extracellular matrix (ECM) organization and require the concerted action of planar cell polarity (PCP) proteins that regulate cell elongation and mediolateral alignment. Data obtained using Xenopus laevis gastrulae have shown that integrin-fibronectin interactions underlie the formation of polarized cell protrusions necessary for PCP and have implicated PCP proteins themselves as regulators of ECM. By contrast, the relationship between establishment of PCP and ECM assembly/remodeling during zebrafish gastrulation is unclear. We previously showed that zebrafish embryos carrying a null mutation in the four-pass transmembrane PCP protein vang-like 2 (vangl2) exhibit increased matrix metalloproteinase activity and decreased immunolabeling of fibronectin. These data implicated for the first time a core PCP protein in the regulation of pericellular proteolysis of ECM substrates and raised the question of whether other zebrafish PCP proteins also impact ECM organization. In Drosophila melanogaster, the cytoplasmic PCP protein Prickle binds Van Gogh and regulates its function. Here we report that similar to vangl2, loss of zebrafish prickle1a decreases fibronectin protein levels in gastrula embryos. We further show that Prickle1a physically binds Vangl2 and regulates both the subcellular distribution and total protein level of Vangl2. These data suggest that the ability of Prickle1a to impact fibronectin organization is at least partly due to effects on Vangl2. In contrast to loss of either Vangl2 or Prickle1a function, we find that glypican4 (a Wnt co-receptor) and frizzled7 mutant gastrula embryos with disrupted non-canonical Wnt signaling exhibit the opposite phenotype, namely increased fibronectin assembly. Our data show that glypican4 mutants do not have decreased proteolysis of ECM substrates, but instead have increased cell surface cadherin protein expression and increased intercellular adhesion. These data indicate that Wnt/Glypican4/Frizzled signaling regulates ECM assembly through effects on cadherin-mediated cell cohesion. Together, our results demonstrate that zebrafish Vangl2/Prickle1a and non-canonical Wnt/Frizzled signaling have opposing effects on ECM organization underlying PCP and gastrulation cell movements.
    Developmental Biology 09/2013; 383(1). DOI:10.1016/j.ydbio.2013.08.027 · 3.55 Impact Factor
Show more

Preview (2 Sources)

9 Reads
Available from