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The Journal of Neuroscience, April 1, 2009, 29(13):3992-4003; doi:10.1523/JNEUROSCI.5237-08.2009

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Development/Plasticity/Repair
BARHL2 Differentially Regulates the Development of Retinal Amacrine and Ganglion Neurons

Qian Ding,^1,2 Hui Chen,⁵ Xiaoling Xie,¹ Richard T. Libby,^1,2 Ning Tian,⁵ and Lin Gan^1,3,4

¹University of Rochester Eye Institute, ²Department of Biomedical Genetics, ³Center for Neural Development and Disease, and ⁴Department of Neurobiology and Anatomy, University of Rochester, Rochester, New York 14642, and ⁵Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut 06520

Correspondence should be addressed to Lin Gan at the above address. Email: lin_gan{at}urmc.rochester.edu

Through transcriptional regulations, the BarH family of homeodomain proteins play essential roles in cell fate specification, cell differentiation, migration, and survival. Barhl2, a member of the Barh gene family, is expressed in retinal ganglion cells (RGCs), amacrine cells (ACs), and horizontal cells. Here, to investigate the role of Barhl2 in retinal development, Barhl2-deficient mice were generated. Analysis of AC subtypes in Barhl2-deficient retinas suggests that Barhl2 plays a critical role in AC subtype determination. A significant reduction of glycinergic and GABAergic ACs with a substantial increase in the number of cholinergic ACs was observed in Barhl2-null retinas. Barhl2 is also critical for the development of a normal complement of RGCs. Barhl2 deficiency resulted in a 35% increase in RGCs undergoing apoptosis during development. Genetic analysis revealed that Barhl2 functions downstream of the Atoh7–Pou4f3 regulatory pathway and regulates the maturation and/or survival of RGCs. Thus, BARHL2 appears to have numerous roles in retinal development, including regulating neuronal subtype specification, differentiation, and survival.

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Received Oct. 28, 2008; revised Jan. 31, 2009; accepted Feb. 12, 2009.

Correspondence should be addressed to Lin Gan at the above address. Email: lin_gan{at}urmc.rochester.edu

This article has been cited by other articles:

				R. A. Poche and B. E. Reese Retinal horizontal cells: challenging paradigms of neural development and cancer biology Development, July 1, 2009; 136(13): 2141 - 2151. [Abstract] [Full Text] [PDF]

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