Eye and neural defects associated with loss of GDF6

BMC Dev Biol. 2006 Sep 29:6:43. doi: 10.1186/1471-213X-6-43.

Abstract

Background: In Xenopus the bone morphogenetic protein growth and differentiation factor 6 (GDF6) is expressed at the edge of the neural plate, and within the anterior neural plate including the eye fields. Here we address the role of GDF6 in neural and eye development by morpholino knockdown experiments.

Results: We show that depletion of GDF6 (BMP13) resulted in a reduction in eye size, loss of laminar structure and a reduction in differentiated neural cell types within the retina. This correlated with a reduction in staining for Smad1/5/8 phosphorylation indicating a decrease in GDF6 signalling through loss of phosphorylation of these intracellular mediators of bone morphogenetic protein (BMP) signalling. In addition, the Pax6 expression domain is reduced in size at early optic vesicle stages. Neural cell adhesion molecule (NCAM) is generally reduced in intensity along the neural tube, while in the retina and brain discreet patches of NCAM expression are also lost. GDF6 knock down resulted in an increase in cell death along the neural tube and within the retina as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.

Conclusion: Our data demonstrate that GDF6 has an important role in neural differentiation in the eye as well as within the central nervous system, and that GDF6 may act in some way to maintain cell survival within the ectoderm, during the normal waves of programmed cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Blotting, Western
  • Bone Morphogenetic Proteins / deficiency
  • Bone Morphogenetic Proteins / genetics*
  • Bone Morphogenetic Proteins / physiology
  • Embryo, Nonmammalian / abnormalities
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • Eye Abnormalities / genetics*
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Gene Expression Regulation, Developmental / genetics*
  • Growth Differentiation Factor 6
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Nervous System / embryology
  • Nervous System / metabolism
  • Nervous System / pathology
  • Nervous System Diseases / embryology
  • Nervous System Diseases / genetics*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Retina / abnormalities
  • Retina / metabolism
  • Xenopus / embryology
  • Xenopus / genetics*
  • Xenopus Proteins / deficiency
  • Xenopus Proteins / genetics
  • Xenopus Proteins / physiology

Substances

  • Bone Morphogenetic Proteins
  • Eye Proteins
  • Growth Differentiation Factor 6
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • RNA, Messenger
  • Repressor Proteins
  • Xenopus Proteins