Dorsal-ventral patterning defects in the eye of BF-1-deficient mice associated with a restricted loss of shh expression

Dev Biol. 1999 Jul 1;211(1):53-63. doi: 10.1006/dbio.1999.9303.

Abstract

Brain factor 1 (BF-1) is a winged-helix transcription factor with restricted expression in the anterior optic vesicle and in the telencephalic neuroepithelium of the neural tube. We have previously found that targeted disruption of the BF-1 gene results in hypoplasia of the cerebral hemispheres, which is more severe in structures derived from the ventral telencephalon. Here we show that the loss of BF-1 leads to multiple developmental anomalies of the eyes. The most ventral structure arising from the optic vesicle, the optic stalk, is missing and is replaced by an expanded retina. Ventral closure of the optic cup and choroid fissure does not occur. These dorsal-ventral patterning defects are not limited to the BF-1-expressing (anterior) cells, but also involve the cells of the posterior optic vesicle. Sonic hedgehog (shh) expression within the ventral telencephalic neuroepithelium is specifically lost in the BF-1(-/-) mutant. Taken together, these findings suggest that shh produced at this site plays a role in patterning the developing eye. This localized deficit in shh expression may also contribute to the prominence of the ventral defects in the telencephalon of the BF-1(-/-) mutant.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Brain / embryology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Eye / embryology*
  • Eye Abnormalities / embryology
  • Eye Abnormalities / genetics
  • Eye Proteins
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Developmental
  • Gene Targeting
  • Hedgehog Proteins
  • Histocytochemistry
  • Homeodomain Proteins*
  • In Situ Hybridization
  • Mice
  • Mice, Knockout
  • Mutation
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • PAX2 Transcription Factor
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Proteins / genetics*
  • Repressor Proteins
  • Retina / embryology
  • Trans-Activators*
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • Eye Proteins
  • Forkhead Transcription Factors
  • Foxd1 protein, mouse
  • Hedgehog Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • PAX2 Transcription Factor
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax2 protein, mouse
  • Pax6 protein, mouse
  • Proteins
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors