Multiple requirements for Hes 1 during early eye formation

Dev Biol. 2005 Aug 15;284(2):464-78. doi: 10.1016/j.ydbio.2005.06.010.

Abstract

During embryogenesis, multiple developmental processes are integrated through their precise temporal regulation. Hes1 is a transcriptional repressor that regulates the timing of mammalian retinal neurogenesis. However, roles for Hes1 in early eye development have not been well defined. Here, we show that Hes1 is expressed in the forming lens, optic vesicle, cup, and pigmented epithelium and is necessary for proper growth, morphogenesis, and differentiation of these tissues. Because Hes1 is required throughout the eye, we investigated its interaction with Pax6. Hes1-Pax6 double mutant embryos are eyeless suggesting these genes are coordinately required for initial morphogenesis and outgrowth of the optic vesicle. In Hes1 mutants, Math5 expression is precocious along with retinal ganglion cell, amacrine, and horizontal neuron formation. In contrast to apparent cooperativity between Pax6 and Hes1 during morphogenesis, each gene regulates Math5 and RGC genesis independently. Together, these studies demonstrate that Hes1, like Pax6, simultaneously regulates multiple developmental processes during optic development.

Publication types

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

MeSH terms

  • Amacrine Cells / cytology
  • Amacrine Cells / embryology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation
  • Embryonic Development
  • Epistasis, Genetic
  • Eye / cytology
  • Eye / embryology*
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Developmental*
  • Helix-Loop-Helix Motifs
  • Heterozygote
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Immunohistochemistry
  • Lens, Crystalline / cytology
  • Lens, Crystalline / embryology
  • Mice
  • Mice, Inbred ICR
  • Mice, Inbred Strains
  • Morphogenesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pigment Epithelium of Eye / cytology
  • Pigment Epithelium of Eye / embryology
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Retina / cytology
  • Retinal Ganglion Cells / cytology
  • Transcription Factor HES-1
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Atoh7 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Eye Proteins
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins
  • Transcription Factor HES-1
  • Transcription Factors