Math3 and NeuroD regulate amacrine cell fate specification in the retina

Development. 2002 Feb;129(4):831-42. doi: 10.1242/dev.129.4.831.


The basic helix-loop-helix genes Math3 and NeuroD are expressed by differentiating amacrine cells, retinal interneurons. Previous studies have demonstrated that a normal number of amacrine cells is generated in mice lacking either Math3 or NEUROD: We have found that, in Math3-NeuroD double-mutant retina, amacrine cells are completely missing, while ganglion and Müller glial cells are increased in number. In the double-mutant retina, the cells that would normally differentiate into amacrine cells did not die but adopted the ganglion and glial cell fates. Misexpression studies using the developing retinal explant cultures showed that, although Math3 and NeuroD alone only promoted rod genesis, they significantly increased the population of amacrine cells when the homeobox gene Pax6 or Six3 was co-expressed. These results indicate that Math3 and NeuroD are essential, but not sufficient, for amacrine cell genesis, and that co-expression of the basic helix-loop-helix and homeobox genes is required for specification of the correct neuronal subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amacrine Cells / cytology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Count
  • Cell Differentiation
  • Culture Techniques
  • Eye Proteins
  • Female
  • Gene Expression
  • Helix-Loop-Helix Motifs*
  • Homeodomain Proteins / genetics
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Repressor Proteins
  • Retina / cytology
  • Retina / growth & development
  • Retina / metabolism
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / metabolism
  • Transcription Factors / genetics


  • Atoh7 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Eye Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neurod4 protein, mouse
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins
  • Sine oculis homeobox homolog 3 protein
  • Transcription Factors
  • Neurogenic differentiation factor 1