Retinal self-organization: a model of retinal ganglion cells and starburst amacrine cells mosaic formation

Open Biol. 2023 Apr;13(4):220217. doi: 10.1098/rsob.220217. Epub 2023 Apr 5.

Abstract

Individual retinal cell types exhibit semi-regular spatial patterns called retinal mosaics. Retinal ganglion cells (RGCs) and starburst amacrine cells (SACs) are known to exhibit such layouts. Mechanisms responsible for the formation of mosaics are not well understood but follow three main principles: (i) homotypic cells prevent nearby cells from adopting the same type, (ii) cell tangential migration and (iii) cell death. Alongside experiments in mouse, we use BioDynaMo, an agent-based simulation framework, to build a detailed and mechanistic model of mosaic formation. We investigate the implications of the three theories for RGC's mosaic formation. We report that the cell migration mechanism yields the most regular mosaics. In addition, we propose that low-density RGC type mosaics exhibit on average low regularities, and thus we question the relevance of regular spacing as a criterion for a group of RGCs to form a RGC type. We investigate SAC mosaics formation and interactions between the ganglion cell layer (GCL) and inner nuclear layer (INL) populations. We propose that homotypic interactions between the GCL and INL populations during mosaics creation are required to reproduce the observed SAC mosaics' characteristics. This suggests that the GCL and INL populations of SACs might not be independent during retinal development.

Keywords: computational modelling; retinal ganglion cells; retinal mosaic; self-organization; starburst amacrine cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amacrine Cells* / metabolism
  • Animals
  • Computer Simulation
  • Mice
  • Retina
  • Retinal Ganglion Cells* / metabolism
  • Software

Associated data

  • figshare/10.6084/m9.figshare.c.6490525