Research article

Temporal order of bipolar cell genesis in the neural retina

Eric M Morrow^1,2* , C-M Amy Chen^3* and Constance L Cepko⁴

¹  Division of Genetics, New Research Building, 77 Avenue Louis Pasteur, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA

²  Department of Psychiatry, 15 Parkman Street, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

³  Novartis Institute for Biomedical Research, 500 Technology Square, Cambridge, MA 02139, USA

⁴  Department of Genetics and Howard Hughes Medical Institute, New Research Building, 77 Avenue Louis Pasteur, Harvard Medical School, Avenue Louis Pasteur, Boston, MA 02115, USA

author email corresponding author email* Contributed equally

Neural Development 2008, 3:2doi:10.1186/1749-8104-3-2

Published:	23 January 2008

Abstract

Background

Retinal bipolar cells comprise a diverse group of neurons. Cone bipolar cells and rod bipolar cells are so named for their connections with cone and rod photoreceptors, respectively. Morphological criteria have been established that distinguish nine types of cone bipolar cells and one type of rod bipolar cell in mouse and rat. While anatomical and physiological aspects of bipolar types have been actively studied, little is known about the sequence of events that leads to bipolar cell type specification and the potential relationship this process may have with synapse formation in the outer plexiform layer. In this study, we have examined the birth order of rod and cone bipolar cells in the developing mouse and rat in vivo.

Results

Using retroviral lineage analysis with the histochemical marker alkaline phosphatase, the percentage of cone and rod bipolar cells born on postnatal day 0 (P0), P4, and P6 were determined, based upon the well characterized morphology of these cells in the adult rat retina. In this in vivo experiment, we have demonstrated that cone bipolar genesis clearly precedes rod bipolar genesis. In addition, in the postnatal mouse retina, using a combination of tritiated-thymidine birthdating and immunohistochemistry to distinguish bipolar types, we have similarly found that cone bipolar genesis precedes rod bipolar genesis. The tritiated-thymidine birthdating studies also included quantification of the birth of all postnatally generated retinal cell types in the mouse.

Conclusion

Using two independent in vivo methodologies in rat and mouse retina, we have demonstrated that there are distinct waves of genesis of the two major bipolar cell types, with cone bipolar genesis preceding rod bipolar genesis. These waves of bipolar genesis correspond to the order of genesis of the presynaptic photoreceptor cell types.