Molecular basis of morphogenesis during vertebrate gastrulation.

Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Cellular and Molecular Life Sciences CMLS (Impact Factor: 5.62). 05/2009; 66(14):2263-73. DOI: 10.1007/s00018-009-0018-2
Source: PubMed

ABSTRACT Gastrulation is a crucial step in early embryogenesis. During gastrulation, a set of morphogenetic processes takes place leading to the establishment of the basic body plan and formation of primary germ layers. A rich body of knowledge about these morphogenetic processes has been accumulated over decades. The understanding of the molecular mechanism that controls the complex cell movement and inductive processes during gastrulation remains a challenge. Substantial progress has been made recently to identify and characterize pathways and molecules implicated in the modulation of morphogenesis during vertebrate gastrulation. Here, we summarize recent findings in the analysis of signaling pathways implicated in gastrulation movements, with the aim to generalize the basic molecular principles of vertebrate morphogenesis.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Metabolic Zonation, i.e. the heterogeneous distribution of different metabolic pathways in different zones of the lobules, forms the basis of proper function of the liver in metabolic homeostasis and its regulation. According to recent results, Metabolic Zonation is controlled by the Wnt/β-catenin signalling pathway. Here, we hypothesize that hedgehog signalling via Indian hedgehog ligands plays an equal share in this control although, up to now, hedgehog signalling is considered not to be active in healthy adult hepatocytes. We provide broad evidence taken mainly by analogy from other mature organs that hedgehog signalling in adult hepatocytes may particularly control liver lipid and cholesterol metabolism as well as certain aspects of hormone biosynthesis. Like Wnt/β-catenin signalling, it seems to act on a very low level forming a porto-central gradient in the lobules opposite to that of Wnt/β-catenin signalling with which it is interacting by mutual inhibition. Consequently, modulation of hegdehog signalling by endogenous and exogenous agents may considerably impact on liver lipid metabolism and beyond. If functioning improperly, it may possibly contribute to diseases like non-alcoholic fatty liver disease (NAFLD) and other diseases such as lipodystrophy.
    Medical Hypotheses 02/2013; 80:589-594. · 1.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gastrulation is a dynamic tissue-remodeling process occurring during early development and fundamental to the later organogenesis. It involves both chemical signals and physical factors. Although much is known about the molecular pathways involved, the roles of physical forces in regulating cellular behavior and tissue remodeling during gastrulation have just begun to be explored. Here, we characterized the force generated by the leading edge mesoderm (LEM) that migrates preceding axial mesoderm (AM), and investigated the contribution of LEM during Xenopus gastrulation. First, we constructed an assay system using micro-needle which could measure physical forces generated by the anterior migration of LEM, and estimated the absolute magnitude of the force to be 20-80nN. Second, laser ablation experiments showed that LEM could affect the force distribution in the AM (i.e. LEM adds stretch force on axial mesoderm along anterior-posterior axis). Third, migrating LEM was found to be necessary for the proper gastrulation cell movements and the establishment of organized notochord structure; a reduction of LEM migratory activity resulted in the disruption of mediolateral cell orientation and convergence in AM. Finally, we found that LEM migration cooperates with Wnt/PCP to form proper notochord. These results suggest that the force generated by the directional migration of LEM is transmitted to AM and assists the tissue organization of notochord in vivo independently of the regulation by Wnt/PCP. We propose that the LEM may have a mechanical role in aiding the AM elongation through the rearrangement of force distribution in the dorsal marginal zone.
    Developmental Biology 08/2013; · 3.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pentachlorophenol (PCP) is a prevalent pollutant in the environment and has been demonstrated to be a serious toxicant to humans and animals. However, little is known regarding the molecular mechanism underlying its toxic effects on vertebrate early development. To explore the impacts and underlying mechanisms of PCP on early development, zebrafish (Danio rerio) embryos were exposed to PCP at concentrations of 0, 20 and 50 μg/l, and microscopic observation and cDNA microarray analysis were subsequently conducted at gastrulation stage. The morphological observations revealed that PCP caused a developmental delay of zebrafish embryos in a concentration-dependent manner. Transcriptomic data showed that 50 μg/l PCP treatment resulted in significant changes in gene expression level, and the genes involved in energy metabolism and cell behavior were identified based on gene functional enrichment analysis. The energy production of embryos was influenced by PCP via the activation of glycolysis along with the inhibition of oxidative phosphorylation (OXPHOS). The results suggested that PCP acts as an inhibitor of OXPHOS at 8 hpf (hours postfertilization). Consistent with the activated glycolysis, the cell cycle activity of PCP-treated embryos was higher than the controls. These characteristics are similar to the Warburg effect, which occurs in human tumors. The microinjection of exogenous ATP confirmed that an additional energy supply could rescue PCP-treated embryos from the developmental delay due to the energy deficit. Taken together, our results demonstrated that PCP causes a Warburg-like effect on zebrafish embryos during gastrulation, and the affected embryos had the phenotype of developmental delay.
    Toxicology and Applied Pharmacology 01/2014; · 3.98 Impact Factor

Full-text (2 Sources)

Available from
Jun 2, 2014

Similar Publications