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Sox2 regulates cholinergic amacrine cell positioning and dendritic stratification in the retina.

Publication ,  Journal Article
Whitney, IE; Keeley, PW; St John, AJ; Kautzman, AG; Kay, JN; Reese, BE
Published in: J Neurosci
July 23, 2014

The retina contains two populations of cholinergic amacrine cells, one positioned in the ganglion cell layer (GCL) and the other in the inner nuclear layer (INL), that together comprise ∼1/2 of a percent of all retinal neurons. The present study examined the genetic control of cholinergic amacrine cell number and distribution between these two layers. The total number of cholinergic amacrine cells was quantified in the C57BL/6J and A/J inbred mouse strains, and in 25 recombinant inbred strains derived from them, and variations in their number and ratio (GCL/INL) across these strains were mapped to genomic loci. The total cholinergic amacrine cell number was found to vary across the strains, from 27,000 to 40,000 cells, despite little variation within individual strains. The number of cells was always lower within the GCL relative to the INL, and the sizes of the two populations were strongly correlated, yet there was variation in their ratio between the strains. Approximately 1/3 of that variation in cell ratio was mapped to a locus on chromosome 3, where Sex determining region Y box 2 (Sox2) was identified as a candidate gene due to the presence of a 6-nucleotide insertion in the protein-coding sequence in C57BL/6J and because of robust and selective expression in cholinergic amacrine cells. Conditionally deleting Sox2 from the population of nascent cholinergic amacrine cells perturbed the normal ratio of cells situated in the GCL versus the INL and induced a bistratifying morphology, with dendrites distributed to both ON and OFF strata within the inner plexiform layer.

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Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

July 23, 2014

Volume

34

Issue

30

Start / End Page

10109 / 10121

Location

United States

Related Subject Headings

  • SOXB1 Transcription Factors
  • Retina
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice, Inbred A
  • Mice, 129 Strain
  • Mice
  • Male
 

Citation

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Whitney, I. E., Keeley, P. W., St John, A. J., Kautzman, A. G., Kay, J. N., & Reese, B. E. (2014). Sox2 regulates cholinergic amacrine cell positioning and dendritic stratification in the retina. J Neurosci, 34(30), 10109–10121. https://doi.org/10.1523/JNEUROSCI.0415-14.2014
Whitney, Irene E., Patrick W. Keeley, Ace J. St John, Amanda G. Kautzman, Jeremy N. Kay, and Benjamin E. Reese. “Sox2 regulates cholinergic amacrine cell positioning and dendritic stratification in the retina.J Neurosci 34, no. 30 (July 23, 2014): 10109–21. https://doi.org/10.1523/JNEUROSCI.0415-14.2014.
Whitney IE, Keeley PW, St John AJ, Kautzman AG, Kay JN, Reese BE. Sox2 regulates cholinergic amacrine cell positioning and dendritic stratification in the retina. J Neurosci. 2014 Jul 23;34(30):10109–21.
Whitney, Irene E., et al. “Sox2 regulates cholinergic amacrine cell positioning and dendritic stratification in the retina.J Neurosci, vol. 34, no. 30, July 2014, pp. 10109–21. Pubmed, doi:10.1523/JNEUROSCI.0415-14.2014.
Whitney IE, Keeley PW, St John AJ, Kautzman AG, Kay JN, Reese BE. Sox2 regulates cholinergic amacrine cell positioning and dendritic stratification in the retina. J Neurosci. 2014 Jul 23;34(30):10109–10121.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

July 23, 2014

Volume

34

Issue

30

Start / End Page

10109 / 10121

Location

United States

Related Subject Headings

  • SOXB1 Transcription Factors
  • Retina
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice, Inbred A
  • Mice, 129 Strain
  • Mice
  • Male