Retinoblastoma (Rb) regulates laminar dendritic arbor reorganization in retinal horizontal neurons.

Abstract

Neuronal differentiation with respect to the acquisition of synaptic competence needs to be regulated precisely during neurogenesis to ensure proper formation of circuits at the right place and time in development. This regulation is particularly important for synaptic triads among photoreceptors, horizontal cells (HCs), and bipolar cells in the retina, because HCs are among the first cell types produced during development, and bipolar cells are among the last. HCs undergo a dramatic transition from vertically oriented neurites that form columnar arbors to overlapping laminar dendritic arbors with differentiation. However, how this process is regulated and coordinated with differentiation of photoreceptors and bipolar cells remains unknown. Previous studies have suggested that the retinoblastoma (Rb) tumor suppressor gene may play a role in horizontal cell differentiation and synaptogenesis. By combining genetic mosaic analysis of individual synaptic triads with neuroanatomic analyses and multiphoton live imaging of developing HCs, we found that Rb plays a cell-autonomous role in the reorganization of horizontal cell neurites as they differentiate. Aberrant vertical processes in Rb-deficient HCs form ectopic synapses with rods in the outer nuclear layer but lack bipolar dendrites. Although previous reports indicate that photoreceptor abnormalities can trigger formation of ectopic synapses, our studies now demonstrate that defects in a postsynaptic partner contribute to the formation of ectopic photoreceptor synapses in the mammalian retina.

• Authors: Rodrigo A P Martins, Denise Davis, Ryan Kerekes, Jiakun Zhang, Ildar T Bayazitov, Daniel Hiler, Mahmut Karakaya, Sharon Frase, Shaun Gleason, Stanislav S Zakharenko, Dianna A Johnson, Michael A Dyer
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 108 Issue 52 Pg. 21111-6 (Dec 27 2011) ISSN: 1091-6490 [Electronic] United States
• PMID: 22160703 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Retinoblastoma Protein

Topics

• Animals
• Cell Differentiation (physiology)
• Dendrites (physiology)
• Mice
• Microscopy, Confocal
• Microscopy, Electron, Transmission
• Neurogenesis (physiology)
• Retinal Horizontal Cells (cytology)
• Retinoblastoma Protein (genetics, metabolism)
• Synapses (physiology)