Satb1 Regulates Contactin 5 to Pattern Dendrites of a Mammalian Retinal Ganglion Cell

Neuron. 2017 Aug 16;95(4):869-883.e6. doi: 10.1016/j.neuron.2017.07.019. Epub 2017 Aug 3.


The size and shape of dendritic arbors are prime determinants of neuronal connectivity and function. We asked how ON-OFF direction-selective ganglion cells (ooDSGCs) in mouse retina acquire their bistratified dendrites, in which responses to light onset and light offset are segregated to distinct strata. We found that the transcriptional regulator Satb1 is selectively expressed by ooDSGCs. In Satb1 mutant mice, ooDSGC dendrites lack ON arbors, and the cells selectively lose ON responses. Satb1 regulates expression of a homophilic adhesion molecule, Contactin 5 (Cntn5). Both Cntn5 and its co-receptor Caspr4 are expressed not only by ooDSGCs, but also by interneurons that form a scaffold on which ooDSGC ON dendrites fasciculate. Removing Cntn5 from either ooDSGCs or interneurons partially phenocopies Satb1 mutants, demonstrating that Satb1-dependent Cntn5 expression in ooDSGCs leads to branch-specific homophilic interactions with interneurons. Thus, Satb1 directs formation of a morphologically and functionally specialized compartment within a complex dendritic arbor.

Keywords: Caspr; Contactin; Satb1; Satb2; dendrite; direction selectivity; hemophilic adhesion; ooDSGC; retinal ganglion cell; starburst amacrine cells.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cadherins / metabolism
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Contactins / metabolism*
  • Dendrites / metabolism*
  • Flow Cytometry
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology
  • HEK293 Cells
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • In Vitro Techniques
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Receptors, Dopamine D4 / genetics
  • Receptors, Dopamine D4 / metabolism
  • Retina / cytology*
  • Retinal Ganglion Cells / cytology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transduction, Genetic
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism


  • Cadherins
  • Cell Adhesion Molecules, Neuronal
  • Contactins
  • Drd4 protein, mouse
  • Homeodomain Proteins
  • Luminescent Proteins
  • Nerve Tissue Proteins
  • Stab1 protein, mouse
  • Transcription Factors
  • Receptors, Dopamine D4
  • Hb9 protein, mouse
  • beta-Galactosidase