title: Modeling activity and target-dependent developmental cell death of mouse retinal ganglion cells ex vivo.
abstract: Programmed cell death is widespread during the development of the central nervous system and serves multiple purposes including the establishment of neural connections. In the mouse retina a substantial reduction of retinal ganglion cells (RGCs) occurs during the first postnatal week, coinciding with the formation of retinotopic maps in the superior colliculus (SC). We previously established a retino-collicular culture preparation which recapitulates the progressive topographic ordering of RGC projections during early post-natal life. Here, we questioned whether this model could also be suitable to examine the mechanisms underlying developmental cell death of RGCs. Brn3a was used as a marker of the RGCs. A developmental decline in the number of Brn3a-immunolabelled neurons was found in the retinal explant with a timing that paralleled that observed in vivo. In contrast, the density of photoreceptors or of starburst amacrine cells increased, mimicking the evolution of these cell populations in vivo. Blockade of neural activity with tetrodotoxin increased the number of surviving Brn3a-labelled neurons in the retinal explant, as did the increase in target availability when one retinal explant was confronted with 2 or 4 collicular slices. Thus, this ex vivo model reproduces the developmental reduction of RGCs and recapitulates its regulation by neural activity and target availability. It therefore offers a simple way to analyze developmental cell death in this classic system. Using this model, we show that ephrin-A signaling does not participate to the regulation of the Brn3a population size in the retina, indicating that eprhin-A-mediated elimination of exuberant projections does not involve developmental cell death.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité mixte de Recherche en Santé 839, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Voyatzis
authors.forename: Aude
authors.initials: A
authors.lastname: Muzerelle
authors.forename: Patricia
authors.initials: P
authors.lastname: Gaspar
authors.forename: Xavier
authors.initials: X
authors.lastname: Nicol
mesh_terms: D025042:Amacrine Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D018920:Coculture Techniques; D055724:Electrophysiological Phenomena / Q000187:drug effects; D036386:Ephrin-A5 / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013477:Superior Colliculi / Q000166:cytology / Q000187:drug effects; D050819:Transcription Factor Brn-3A / Q000378:metabolism
chemical_list: D036386:Ephrin-A5; C494189:Pou4f1 protein, mouse; D050819:Transcription Factor Brn-3A