A balance between the anti-apoptotic activity of Slug and the apoptotic activity of msx1 is required for the proper development of the neural crest

Dev Biol. 2004 Nov 15;275(2):325-42. doi: 10.1016/j.ydbio.2004.07.041.

Abstract

We have studied the pattern of programmed cell death in the neural crest and analyzed how it is controlled by the activity of the transcription factors Slug and msx1. Our results indicate that apoptosis is more prevalent in the neural folds than in the rest of the neural ectoderm. Through gain- and loss-of-function experiments with inducible forms of both Slug and msx1 genes, we showed that Slug acts as an anti-apoptotic factor whereas msx1 promotes cell death, either in the neural folds of the whole embryos, in isolated or induced neural crest and in animal cap assays. The protective effect of expressing Slug can be reversed by expressing the apoptotic factor Bax, while the apoptosis promoted by msx1 can be abolished by expressing the Xenopus homologue of Bcl2 (XR11). Furthermore, we show that Slug and msx1 control the transcription of XR11 and several caspases required for programmed cell death. In addition, expression of Bax or Bcl2, produced similar effects on the survival of the neural crest and on the development of its derivatives to those produced by altering the activity of Slug or msx1. Finally, we show that in the neural crest, the region of the neural folds where Slug is expressed, cells undergo less apoptosis, than in the region where the msx1 gene is expressed, which correspond to cells adjacent to the neural crest. We show that the expression of Slug and msx1 controls cell death in certain areas of the neural folds, and we discuss how this equilibrium is necessary to generate sharp boundaries in the neural crest territory, and to precisely control cell number among neural crest derivatives.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Carrier Proteins
  • Cell Proliferation
  • DNA Fragmentation / genetics
  • DNA Primers
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / metabolism*
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • MSX1 Transcription Factor
  • Microinjections
  • Neural Crest / embryology*
  • Neural Crest / metabolism
  • Plasmids / genetics
  • Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Snail Family Transcription Factors
  • Transcription Factors / metabolism*
  • Xenopus Proteins
  • Xenopus laevis / embryology*
  • bcl-2-Associated X Protein

Substances

  • Carrier Proteins
  • DNA Primers
  • Homeodomain Proteins
  • MSX1 Transcription Factor
  • MSX1 protein, Xenopus
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Snail Family Transcription Factors
  • Transcription Factors
  • Xenopus Proteins
  • bcl-2-Associated X Protein
  • noggin protein