title: Biasing amacrine subtypes in the Atoh7 lineage through expression of Barhl2.
abstract: Within the developing vertebrate retina, particular subtypes of amacrine cells (ACs) tend to arise from progenitors expressing the basic helix-loop-helix (bHLH) transcription factor, Atoh7, which is necessary for the early generation of retinal ganglion cells (RGCs). All ACs require the postmitotic expression of the bHLH pancreas transcription factor Ptf1a; however, Ptf1a alone is not sufficient to give subtype identities. Here we use functional and in vivo time-lapse studies in the zebrafish retina to investigate on the developmental programs leading to ACs specification within the subsequent divisions of Atoh7-positive progenitors. We find evidences that the homeobox transcription factor Barhl2 is an AC subtype identity-biasing factor that turns on within Atoh7-positive descendants. In vivo lineage tracing reveals that particular modes of cell division tend to generate Barhl2-positive precursors from sisters of RGCs. Additionally, Atoh7 indirectly impacts these division modes to regulate the right number of barhl2-expressing cells. We finally find that Atoh7 itself influences the subtypes of Barhl2-dependent ACs. Together, the results from our study uncover lineage-related and molecular logic of subtype specification in the vertebrate retina, by showing that specific AC subtypes arise via a particular mode of cell division and a transcriptional network cascade involving the sequential expression of first atoh7 followed by ptf1a and then barhl2.
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, Victoria 3800, Australia.
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Jusuf
authors.forename: Shahad
authors.initials: S
authors.lastname: Albadri
authors.forename: Alessio
authors.initials: A
authors.lastname: Paolini
authors.forename: Peter D
authors.initials: PD
authors.lastname: Currie
authors.forename: Francesco
authors.initials: F
authors.lastname: Argenton
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Higashijima
authors.forename: William A
authors.initials: WA
authors.lastname: Harris
authors.forename: Lucia
authors.initials: L
authors.lastname: Poggi
mesh_terms: D025042:Amacrine Cells / Q000145:classification / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D002455:Cell Division; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018257:Helix-Loop-Helix Motifs / Q000502:physiology; D008297:Male; D060172:Morpholinos / Q000494:pharmacology; D012160:Retina / Q000196:embryology; D059008:Time-Lapse Imaging; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: C577478:Barhl2 protein, zebrafish; D004268:DNA-Binding Proteins; D060172:Morpholinos; D014157:Transcription Factors; D029961:Zebrafish Proteins; C413414:atoh7 protein, zebrafish; C062602:transcription factor PTF1