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Proc Natl Acad Sci U S A. 2017 May 16;114(20):E3974-E3983. doi: 10.1073/pnas.1618551114. Epub 2017 May 2.

Molecular codes for cell type specification in Brn3 retinal ganglion cells.

Author information

1
Retinal Circuits Development and Genetics Unit, Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, Bethesda, MD 20892.
2
Genomics Core, Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, Bethesda, MD 20892.
3
Ocular Gene Therapy Core, National Eye Institute, Bethesda, MD 20892.
4
Institute of Biology, Romanian Academy, Bucharest 060031, Romania.
5
Molecular Biology Center, Interdisciplinary Research Institute on Bio-Nano-Science, Babes-Bolyai University, Cluj-Napoca 400084, Romania.
6
Retinal Circuits Development and Genetics Unit, Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, Bethesda, MD 20892; badeatc@mail.nih.gov.

Abstract

Visual information is conveyed from the eye to the brain by distinct types of retinal ganglion cells (RGCs). It is largely unknown how RGCs acquire their defining morphological and physiological features and connect to upstream and downstream synaptic partners. The three Brn3/Pou4f transcription factors (TFs) participate in a combinatorial code for RGC type specification, but their exact molecular roles are still unclear. We use deep sequencing to define (i) transcriptomes of Brn3a- and/or Brn3b-positive RGCs, (ii) Brn3a- and/or Brn3b-dependent RGC transcripts, and (iii) transcriptomes of retinorecipient areas of the brain at developmental stages relevant for axon guidance, dendrite formation, and synaptogenesis. We reveal a combinatorial code of TFs, cell surface molecules, and determinants of neuronal morphology that is differentially expressed in specific RGC populations and selectively regulated by Brn3a and/or Brn3b. This comprehensive molecular code provides a basis for understanding neuronal cell type specification in RGCs.

KEYWORDS:

Pou4f1; Pou4f2; neuronal cell types; retinal ganglion cells; transcription factors

PMID:
28465430
PMCID:
PMC5441800
DOI:
10.1073/pnas.1618551114
[Indexed for MEDLINE]
Free PMC Article

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