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Similarities and differences among inner retinal neurons revealed by the expression of reporter transgenes controlled by Brn-3a, Brn-3b, and Brn-3c promotor sequences

Published online by Cambridge University Press:  02 June 2009

Mengqing Xiang ,
Lijuan Zhou  and
Jeremy Nathans
Mengqing Xiang
Affiliation:
Department of Molecular Biology and Genetics Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore
Lijuan Zhou
Affiliation:
Department of Molecular Biology and Genetics Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore
Jeremy Nathans
Affiliation:
Department of Molecular Biology and Genetics Neuroscience Ophthalmology Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore
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Abstract

Brn-3a, Brn-3b, and Brn-3c are highly homologous POU-domain transcription factors that are expressed in subsets of retinal ganglion cells. From each of the mouse Brn-3 genes, a DNA segment ranging in size from 4.6 to 13.4 kb and located immediately upstream of the start site of translation was joined to a human placental alkaline phosphatase (AP) reporter cDNA. Following the introduction of each construct into the mouse germline, a total of 19 transgenic lines were obtained, of which 16 expressed the AP reporter in the retina. Unexpectedly, at least 14 of the 16 expressing lines showed AP activity in subsets of amacrine cells, and these subsets typically differed among mouse lines injected with the same construct. Transgene expression was also found in ganglion cells in four lines and bipolar cells in seven lines. In all cases AP activity was confined to cells in the inner nuclear layer and the ganglion cell layer. The expression of Brn-3 transgenes in multiple cell types in the inner retina is reminiscent of earlier experiments in which visual pigment transgenes were found to be expressed in multiple cell types in the outer retina. Taken together, these observations suggest that anatomically and/or functionally related retinal neurons contain partially overlapping transcriptional regulatory specificities.

Keywords

Transgenic miceAmacrine cellsRetinaPOU-domain transcription factors

Information

Type
Research Articles
Information
Visual Neuroscience , Volume 13 , Issue 5 , September 1996 , pp. 955 - 962
Copyright
Copyright © Cambridge University Press 1996

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References

Adler, R. & Hatlee, M. (1989). Plasticity and differentiation of embryonic retinal cells after terminal mitosis. Science 243, 391–393.CrossRefGoogle ScholarPubMed
Altshuler, D., Lo Turco, J.J., Rush, J. & Cepko, C. (1993). Taurine promotes the differentiation of a vertebrate retinal cell type in vitro. Development 199, 1317–1328.CrossRefGoogle Scholar
Berger, J., Howard, A.D., Gerber, L., Cullen, B.R. & Udenfriend, S. (1987). Expression of active, membrane-bound human placental alkaline phosphatase by transfected simian cells. Proceedings of the National Academy of Sciences of the U.S.A. 84, 4885–4889.CrossRefGoogle ScholarPubMed
Chen, J., Tucker, C.L., Woodford, B., Szel, A., Lem, J., Gianella-Borradori, A., Simon, M.I. & Bogenmann, E. (1994). The human blue opsin promotor directs transgene expression in short-wave cones and bipolar cells in the mouse retina. Proceedings of the National Academy of Sciences of the U.S.A. 91, 2611–2615.CrossRefGoogle Scholar
Chiu, I. & Nathans, J. (1994). Blue cones and cone bipolar cells share transcriptional specificity as determined by expression of human blue visual pigment-derived transgenes. Journal of Neuroscience 14, 3426–3436.CrossRefGoogle ScholarPubMed
Dowling, J.E. (1987). The Retina: An Approachable Part of the Brain. Cambridge, Massachusetts: Harvard Press.Google Scholar
Fields-Barry, S.C., Halliday, A.L. & Cepko, C.L. (1992). A recom-binant retrovirus encoding alkaline phosphatase confirms clonal boundary assignment in lineage analysis of murine retina. Proceedings of the National Academy of Sciences of the U.S.A. 89, 693–697.CrossRefGoogle Scholar
Frischauf, A.-M., Lehrach, H., Poustka, A. & Murray, N. (1983). Lambda replacement vectors carrying polylinker sequences. Journal of Molecular Biology 170, 827–842.CrossRefGoogle ScholarPubMed
Gerrero, M.R., McEvilly, R., Turner, E., Lin, C.R., O'Connell, S., Jenne, K.J., Hobbs, M.V. & Rosenfeld, M.G. (1993). Brn-3.0: a POU-domain protein expressed in the sensory, immune, and endocrine systems that functions on elements distinct from known octamer motifs. Proceedings of the National Academy of Sciences of the U.S.A. 90, 10841–10845.CrossRefGoogle ScholarPubMed
Hogan, B., Constantini, F. & Lacy, E. (1986). Manipulating the Mouse Genome. New York: Cold Spring Harbor Laboratory.Google Scholar
Holt, C.E., Bertsch, T.W., Ellis, H.M. & Harris, W.A. (1988). Cellular determination in the Xenopus retina is independent of lineage and birth data. Neuron 1, 15–26.CrossRefGoogle Scholar
Kolb, H. (1994). The architecture of functional neural circuits in the vertebrate retina. Investigative Ophthalmology and Visual Science 35, 2385–2404.Google ScholarPubMed
Peschon, J.J., Behringer, R.R., Brinster, R.L. & Palmiter, R.D. (1987). Spermatid-specific expression of protamine 1 in transgenic mice. Proceedings of the National Academy of Sciences of the U.S.A. 84, 5316–5319.CrossRefGoogle ScholarPubMed
Rodieck, R.W. (1973). The Vertebrate Retina: Principles of Structure and function. New York: Freeman Press.Google Scholar
Rodieck, R.W. (1988). The primate retina. Comparative Primate Biology 4, 203–278.Google Scholar
Sidman, R.L. (1961). Histogenesis of mouse retina studied with thymidine-3H. In The Structure of the Eye, ed. Smelser, G., pp. 487–506. New York: Academic Press.Google Scholar
Theil, T., Zechner, U., Klett, C., Adolph, S. & Moroy, T. (1994). Chromosomal localization and sequences of the murine Brn-3 family of developmental control genes. Cytogenetics and Cell Genetics 66, 267–271.CrossRefGoogle ScholarPubMed
Turner, D.L., Snyder, E.Y. & Cepko, C.L. (1990). Lineage independent determination of cell type in the embryonic mouse retina. Neuron 4, 833–845.CrossRefGoogle ScholarPubMed
Turner, E.E., Jenne, K.J. & Rosenfeld, M.G. (1994). Brn-3.2: A Brn-3-related transcription factor with distinctive central nervous system expression and regulation by retinoic acid. Neuron 12, 205–218.CrossRefGoogle ScholarPubMed
Wang, Y., Macke, J.P., Merbs, S.L., Klaunberg, B., Bennett, J., Zack, D., Gearhart, J. & Nathans, J. (1992). A locus control region adjacent to the human red and green pigment genes. Neuron 9, 429–440.CrossRefGoogle Scholar
Wässle, H. & Boycott, B.B. (1991). Functional architecture of the mammalian retina. Physiological Reviews 71, 447–479.CrossRefGoogle ScholarPubMed
Wetts, R. & Fraser, S.E. (1988). Multipotent precursors can give rise to all major cell types of the frog retina. Science 239, 1142–1145.CrossRefGoogle ScholarPubMed
Woodford, B.J., Chen, J. & Simon, M.I. (1994). Expression of rho-dopsin promotor transgene product in both rods and cones. Experimental Eye Research 58, 631–635.CrossRefGoogle Scholar
Xiang, M., Zhou, L., Peng, Y.-W., Eddy, R.L., Shows, T.B. & Nathans, J. (1993). Brn-3b: A POU-domain protein expressed in a subset of retinal ganglion cells. Neuron 11, 689–701.CrossRefGoogle Scholar
Xiang, M., Zhou, L., Macke, J.P., Yoshioka, T., Hendry, S.H.C., Eddy, R.L., Shows, T.B. & Nathans, J. (1995). The Brn-3 family of POU-domain factors: Primary structure, binding specificity, and expression in subsets of retinal ganglion cells and somatosensory neurons. Journal of Neuroscience 15, 4762–4785.CrossRefGoogle ScholarPubMed
Young, R. (1985). Cell differentiation in the retina of the mouse. Anatomical Record 212, 199–205.CrossRefGoogle ScholarPubMed
Zack, D.J., Bennett, J., Wang, Y., Davenport, C., Klaunberg, B., Gearhart, J. & Nathans, J. (1991). Unusual topography of bovine rhodopsin promoter-lacZ fusion gene expression in transgenic mouse retinas. Neuron 6, 187–199.CrossRefGoogle ScholarPubMed