Transient requirement for ganglion cells during assembly of retinal synaptic layers

Development. 2004 Mar;131(6):1331-42. doi: 10.1242/dev.01040. Epub 2004 Feb 18.

Abstract

The inner plexiform layer (IPL) of the vertebrate retina comprises functionally specialized sublaminae, representing connections between bipolar, amacrine and ganglion cells with distinct visual functions. Developmental mechanisms that target neurites to the correct synaptic sublaminae are largely unknown. Using transgenic zebrafish expressing GFP in subsets of amacrine cells, we imaged IPL formation and sublamination in vivo and asked whether the major postsynaptic cells in this circuit, the ganglion cells, organize the presynaptic inputs. We found that in the lak/ath5 mutant retina, where ganglion cells are never born, formation of the IPL is delayed, with initial neurite outgrowth ectopically located and grossly disorganized. Over time, the majority of early neurite projection errors are corrected, and major ON and OFF sublaminae do form. However, focal regions of disarray persist where sublaminae do not form properly. Bipolar axons, which arrive later, are targeted correctly, except at places where amacrine stratification is disrupted. The lak mutant phenotype reveals that ganglion cells have a transient role organizing the earliest amacrine projections to the IPL. However, it also suggests that amacrine cells interact with each other during IPL formation; these interactions alone appear sufficient to form the IPL. Furthermore, our results suggest that amacrines may guide IPL sublamination by providing stratification cues for other cell types.

Publication types

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

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic
  • Eye Proteins
  • Genes, Reporter
  • Growth Substances / genetics
  • Growth Substances / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mutation
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins
  • Retina / embryology*
  • Retinal Ganglion Cells*
  • Zebrafish / embryology
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • Eye Proteins
  • Growth Substances
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Zebrafish Proteins
  • atoh7 protein, zebrafish