Postnatal developmental dynamics of cell type specification genes in Brn3a/Pou4f1 Retinal Ganglion Cells

Autor: Tudor C. Badea, Matthew Brooks, Vladimir Vladimirovich Muzyka
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Retinal Ganglion Cells
Candidate gene
genetic structures
lcsh:RC346-429
Mice
0302 clinical medicine
Mitogen-Activated Protein Kinase 10
Synapse formation
Retinal ganglion cell
Dendrite formation
Transcription Factor Brn-3A
Age Factors
Gene Expression Regulation
Developmental
RNA sequencing
Cadherins
Cell biology
medicine.anatomical_structure
Female
Research Article
Cell type
Subtype specification
Nerve Tissue Proteins
In situ hybridization
Biology
Retinal ganglion
Retina
Statistics
Nonparametric
03 medical and health sciences
Developmental Neuroscience
medicine
Animals
RNA
Messenger
Eye Proteins
Ganglion cell layer
lcsh:Neurology. Diseases of the nervous system
Homeodomain Proteins
Tumor Suppressor Proteins
Brn3a
Membrane Proteins
eye diseases
Mice
Inbred C57BL
Postnatal development
030104 developmental biology
Animals
Newborn
sense organs
in situ hybridization
Developmental biology
030217 neurology & neurosurgery
Transcription Factors
Zdroj: Neural Development
Neural Development, Vol 13, Iss 1, Pp 1-33 (2018)
ISSN: 1749-8104
Popis: Background About 20–30 distinct Retinal Ganglion Cell (RGC) types transmit visual information from the retina to the brain. The developmental mechanisms by which RGCs are specified are still largely unknown. Brn3a is a member of the Brn3/Pou4f transcription factor family, which contains key regulators of RGC postmitotic specification. In particular, Brn3a ablation results in the loss of RGCs with small, thick and dense dendritic arbors (‘midget-like’ RGCs), and morphological changes in other RGC subpopulations. To identify downstream molecular mechanisms underlying Brn3a effects on RGC numbers and morphology, our group recently performed a RNA deep sequencing screen for Brn3a transcriptional targets in mouse RGCs and identified 180 candidate transcripts. Methods We now focus on a subset of 28 candidate genes encoding potential cell type determinant proteins. We validate and further define their retinal expression profile at five postnatal developmental time points between birth and adult stage, using in situ hybridization (ISH), RT-PCR and fluorescent immunodetection (IIF). Results We find that a majority of candidate genes are enriched in the ganglion cell layer during early stages of postnatal development, but dynamically change their expression profile. We also document transcript-specific expression differences for two example candidates, using RT-PCR and ISH. Brn3a dependency could be confirmed by ISH and IIF only for a fraction of our candidates. Conclusions Amongst our candidate Brn3a target genes, a majority demonstrated ganglion cell layer specificity, however only around two thirds showed Brn3a dependency. Some were previously implicated in RGC type specification, while others have known physiological functions in RGCs. Only three genes were found to be consistently regulated by Brn3a throughout postnatal retina development – Mapk10, Tusc5 and Cdh4. Electronic supplementary material The online version of this article (10.1186/s13064-018-0110-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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