Cellular patterns in the inner retina of adult zebrafish: Quantitative analyses and a computational model of their formation

Abstract

The mechanisms that control cellular pattern formation in the growing vertebrate central nervous system are poorly understood. In an effort to reveal mechanistic rules of cellular pattern formation in the central nervous system, quantitative spatial analysis and computational modeling techniques were applied to cellular patterns in the inner retina of the adult zebrafish. All the analyzed cell types were arrayed in nonrandom patterns tending toward regularity; specifically, they were locally anticlustered. Over relatively large spatial scales, only one cell type exhibited consistent evidence for pattern regularity, suggesting that cellular pattern formation in the inner retina is dominated by local anticlustering mechanisms. Cross-correlation analyses revealed independence between the patterns of different cell types, suggesting that cellular pattern formation may involve multiple, independent, homotypic anticlustering mechanisms. A computational model of cellular pattern formation in the growing zebrafish retina was developed, which featured an inhibitory, homotypic signaling mechanism, arising from differentiated cells, that controlled the spatial profile of cell fate decisions. By adjusting the spatial profile of this decaying-exponential signal, the model provided good estimates of all the cellular patterns that were observed in vivo, as objectively judged by quantitative spatial pattern analyses. The results support the hypothesis that cellular pattern formation in the inner retina of zebrafish is dominated by a set of anticlustering mechanisms that may control events at, or near, the spatiotemporal point of cell fate decision.