Morphologies of mouse retinal ganglion cells expressing transcription factors Brn3a, Brn3b, and Brn3c: Analysis of wild type and mutant cells using genetically-directed sparse labeling

Morphologies of mouse retinal ganglion cells visualized by sparse genetic activation of an alkaline phosphatase reporter targeted to the Brn3a, Brn3b, or Brn3c loci. Retinal ganglion cells were traced using Neuromantic software and are show en face and in cross section. Colored boundaries indicate the morphologic types characteristic for retinal ganglion cells expressing the indicated Brn3 family member. [Display omitted] ► Sparse genetic recombination of Brn3 transcription factor knock-in reporter alleles reveals retinal ganglion cell dendritic arbor morphologies. ► Brn3a, Brn3b and Brn3c are expressed in distinct but overlapping RGC type populations. ► When sparsely inactivated in individual RGCs, ablation of Brn3b leads mostly to axonal defects and some dendritic arbor deficiencies. ► Sparse ablation of Brn3a leads to dendritic arbor defects, whereas ablation of Brn3c does not affect RGC dendritic or axonal arbor formation. The mammalian retina contains more than 50 distinct neuronal types, which are broadly classified into several major classes: photoreceptor, bipolar, horizontal, amacrine, and ganglion cells. Although some of the developmental mechanisms involved in the differentiation of retinal ganglion cells (RGCs) are beginning to be understood, there is little information regarding the genetic and molecular determinants of the distinct morphologies of the 15–20 mammalian RGC cell types. Previous work has shown that the transcription factor Brn3b/Pou4f2 plays a major role in the development and survival of many RGCs. The roles of the closely related family members, Brn3a/Pou4f1 and Brn3c/Pou4f3 in RGC development are less clear. Using a genetically-directed method for sparse cell labeling and sparse conditional gene ablation in mice, we describe here the sets of RGC types in which each of the three Brn3/Pou4f transcription factors are expressed and the consequences of ablating these factors on the development of RGC morphologies.