Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors

Masayuki Akimoto; Hong Cheng; Dongxiao Zhu; Joseph A. Brzezinski; Ritu Khanna; Elena Filippova; Edwin C T Oh; Yuezhou Jing; Jose Luis Linares; Matthew Brooks; Sepideh Zareparsi; Alan J. Mears; Alfred Hero; Thomas M Glaser; Anand Swaroop

doi:10.1073/pnas.0508214103

Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors

Masayuki Akimoto, Hong Cheng, Dongxiao Zhu, Joseph A. Brzezinski, Ritu Khanna, Elena Filippova, Edwin C T Oh, Yuezhou Jing, Jose Luis Linares, Matthew Brooks, Sepideh Zareparsi, Alan J. Mears, Alfred Hero, Thomas M Glaser, Anand Swaroop

Research output: Contribution to journal › Article

210 Scopus citations

Abstract

The Maf-family transcription factor Nrl is a key regulator of photoreceptor differentiation in mammals. Ablation of the Nrl gene in mice leads to functional cones at the expense of rods. We show that a 2.5-kb Nrl promoter segment directs the expression of enhanced GFP specifically to rod photoreceptors and the pineal gland of transgenic mice, GFP is detected shortly after terminal cell division, corresponding to the timing of rod genesis revealed by birthdating studies. In Nrl^-/- retinas, the GFP+ photoreceptors express S-opsin, consistent with the transformation of rod precursors into cones. We report the gene profiles of freshly isolated flow-sorted GFP+ photoreceptors from wild-type and Nrl^-/- retinas at five distinct developmental stages. Our results provide a framework for establishing gene regulatory networks that lead to mature functional photoreceptors from postmitotic precursors. Differentially expressed rod and cone genes are excellent candidates for retinopathies.

Original language	English (US)
Pages (from-to)	3890-3895
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	103
Issue number	10
DOIs	https://doi.org/10.1073/pnas.0508214103
State	Published - Mar 7 2006
Externally published	Yes

Keywords

Gene profiling
Gene regulation
Neuronal differentiation
Retina
Transcription factor

ASJC Scopus subject areas

Genetics
General

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10.1073/pnas.0508214103

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Akimoto, M., Cheng, H., Zhu, D., Brzezinski, J. A., Khanna, R., Filippova, E., Oh, E. C. T., Jing, Y., Linares, J. L., Brooks, M., Zareparsi, S., Mears, A. J., Hero, A., Glaser, T. M., & Swaroop, A. (2006). Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors. Proceedings of the National Academy of Sciences of the United States of America, 103(10), 3890-3895. https://doi.org/10.1073/pnas.0508214103

Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors. / Akimoto, Masayuki; Cheng, Hong; Zhu, Dongxiao; Brzezinski, Joseph A.; Khanna, Ritu; Filippova, Elena; Oh, Edwin C T; Jing, Yuezhou; Linares, Jose Luis; Brooks, Matthew; Zareparsi, Sepideh; Mears, Alan J.; Hero, Alfred; Glaser, Thomas M; Swaroop, Anand.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 10, 07.03.2006, p. 3890-3895.

Research output: Contribution to journal › Article

Akimoto, M, Cheng, H, Zhu, D, Brzezinski, JA, Khanna, R, Filippova, E, Oh, ECT, Jing, Y, Linares, JL, Brooks, M, Zareparsi, S, Mears, AJ, Hero, A, Glaser, TM & Swaroop, A 2006, 'Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors', Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 10, pp. 3890-3895. https://doi.org/10.1073/pnas.0508214103

Akimoto, Masayuki ; Cheng, Hong ; Zhu, Dongxiao ; Brzezinski, Joseph A. ; Khanna, Ritu ; Filippova, Elena ; Oh, Edwin C T ; Jing, Yuezhou ; Linares, Jose Luis ; Brooks, Matthew ; Zareparsi, Sepideh ; Mears, Alan J. ; Hero, Alfred ; Glaser, Thomas M ; Swaroop, Anand. / Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 10. pp. 3890-3895.

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abstract = "The Maf-family transcription factor Nrl is a key regulator of photoreceptor differentiation in mammals. Ablation of the Nrl gene in mice leads to functional cones at the expense of rods. We show that a 2.5-kb Nrl promoter segment directs the expression of enhanced GFP specifically to rod photoreceptors and the pineal gland of transgenic mice, GFP is detected shortly after terminal cell division, corresponding to the timing of rod genesis revealed by birthdating studies. In Nrl-/- retinas, the GFP+ photoreceptors express S-opsin, consistent with the transformation of rod precursors into cones. We report the gene profiles of freshly isolated flow-sorted GFP+ photoreceptors from wild-type and Nrl-/- retinas at five distinct developmental stages. Our results provide a framework for establishing gene regulatory networks that lead to mature functional photoreceptors from postmitotic precursors. Differentially expressed rod and cone genes are excellent candidates for retinopathies.",

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AU - Filippova, Elena

AU - Oh, Edwin C T

AU - Jing, Yuezhou

AU - Linares, Jose Luis

AU - Brooks, Matthew

AU - Zareparsi, Sepideh

AU - Mears, Alan J.

AU - Hero, Alfred

AU - Glaser, Thomas M

AU - Swaroop, Anand

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AB - The Maf-family transcription factor Nrl is a key regulator of photoreceptor differentiation in mammals. Ablation of the Nrl gene in mice leads to functional cones at the expense of rods. We show that a 2.5-kb Nrl promoter segment directs the expression of enhanced GFP specifically to rod photoreceptors and the pineal gland of transgenic mice, GFP is detected shortly after terminal cell division, corresponding to the timing of rod genesis revealed by birthdating studies. In Nrl-/- retinas, the GFP+ photoreceptors express S-opsin, consistent with the transformation of rod precursors into cones. We report the gene profiles of freshly isolated flow-sorted GFP+ photoreceptors from wild-type and Nrl-/- retinas at five distinct developmental stages. Our results provide a framework for establishing gene regulatory networks that lead to mature functional photoreceptors from postmitotic precursors. Differentially expressed rod and cone genes are excellent candidates for retinopathies.

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