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Publication : Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity.

First Author  West ER Year  2022
Journal  Cell Rep Volume  38
Issue  1 Pages  110191
PubMed ID  34986354 Mgi Jnum  J:324792
Mgi Id  MGI:6874528 Doi  10.1016/j.celrep.2021.110191
Citation  West ER, et al. (2022) Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity. Cell Rep 38(1):110191
abstractText  How do neuronal subtypes emerge during development? Recent molecular studies have profiled existing neuronal diversity, but neuronal subtype genesis remains elusive. The 15 types of mouse retinal bipolar interneurons are characterized by distinct functions, morphologies, and transcriptional profiles. Here, we develop a comprehensive spatiotemporal map of bipolar subtype genesis in the murine retina. Combining multiplexed detection of 16 RNA markers with timed delivery of 5-ethynyl uridine (EdU) and bromodeoxyuridine (BrdU), we analyze more than 30,000 single cells in full retinal sections to classify all bipolar subtypes and their birthdates. We find that bipolar subtype birthdates are ordered and follow a centrifugal developmental axis. Spatial analysis reveals a striking wave pattern of bipolar subtype birthdates, and lineage analyses suggest clonal restriction on homotypic subtype production. These results inspire a hierarchical developmental model, with ordered subtype genesis within lineages. Our results provide insight into neuronal subtype development and establish a framework for studying subtype diversification.
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