The function of Xenopus germ cell nuclear factor (xGCNF) in morphogenetic movements during neurulation

Dev Biol. 2003 May 15;257(2):329-42. doi: 10.1016/s0012-1606(03)00109-x.

Abstract

The germ cell nuclear factor (GCNF, NR6A1) is a nuclear orphan receptor first described in the mouse testis and subsequently identified as an essential transcription factor in vertebrate embryogenesis. Here, we analyze the phenotype of Xenopus embryos after depletion of embryonic GCNF (xEmGCNF) protein using a specific morpholino antisense oligonucleotide. Morphological defects after xEmGCNF knockdown became obvious from neurulation onward. Among the abnormalities observed, defective formation of the neural tube and a short and curved main body axis were the most remarkable traits. Histological analysis, lineage tracing of injected blastomeres, and Keller sandwich explants revealed that xEmGCNF function is required for different patterns of cell intercalation during neurulation and consequently for the sequence of morphogenetic movements leading to formation of the neural tube. Further characterization of the phenotype at the molecular level showed an abnormal distribution of the extracellular matrix protein fibronectin and a reduction in the expression level of the integrin subunits alpha5 and alpha6, the limiting components of the laminin and fibronectin receptors, respectively. We propose integrin-mediated cell-matrix interaction as a process that requires xEmGCNF function and provides, in concert with cadherins-mediated cell-cell interactions, a molecular basis for morphogenetic cell movements during neurulation.

MeSH terms

  • Animals
  • Blastomeres
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Embryo, Nonmammalian / drug effects
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism
  • Fibronectins / metabolism
  • Gene Expression Regulation, Developmental
  • Head / abnormalities
  • Head / embryology
  • Integrin alpha5 / genetics
  • Integrin alpha6 / genetics
  • Morphogenesis / drug effects
  • Nervous System / embryology*
  • Nervous System / pathology
  • Neural Tube Defects / chemically induced
  • Neural Tube Defects / genetics
  • Neural Tube Defects / pathology
  • Nuclear Receptor Subfamily 6, Group A, Member 1
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology
  • Phenotype
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Transplants
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / embryology*
  • Xenopus laevis / genetics

Substances

  • DNA-Binding Proteins
  • Fibronectins
  • Integrin alpha5
  • Integrin alpha6
  • Nr6a1 protein, mouse
  • Nuclear Receptor Subfamily 6, Group A, Member 1
  • Oligonucleotides, Antisense
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • Xenopus Proteins