DCC is specifically required for the survival of retinal ganglion and displaced amacrine cells in the developing mouse retina.

Ming Shi, Min-Hua Zheng, Zhi-Rong Liu, Ze-Lan Hu, Ying Huang, Jia-Yin Chen, Gang Zhao, Hua Han, Yu-Qiang Ding

Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, China.

Developmental biology 2010 Dec 1

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Netrin-1 and DCC are well known for their roles in neurite growth, axonal guidance, and neuronal migration. Recently, a number of studies showed that DCC is involved in the induction of apoptosis, and this proapoptotic activity can be blocked in the presence of Netrin-1. However, here, we found that DCC is required for the survival of two types of neurons selectively in the developing mouse retina where DCC is abundantly expressed. Our results showed that the DCC(-/-) retina displayed a reduced ganglion cell layer with relatively normal neuroblastic layer. Immunostaining assays revealed that in DCC(-/-) mice, initial neurogenesis within retina was unchanged while the numbers of differentiated retinal ganglion cells and displaced amacrine cells in ganglion cell layer were greatly reduced due to increased apoptosis. By contrast, other neuronal types including horizontal cells, bipolar cells, amacrine cells, photoreceptors, and Müller cells appeared normal in DCC mutant retinas. Moreover, DCC(kanga) mice that lack the intracellular P3 domain of DCC receptor displayed the same defects as DCC(-/-) mice. Thus, our findings suggest that DCC is a key regulator for the survival of specific types of neurons during retinal development and that DCC-P3 domain is essential for this developing event. Copyright © 2010 Elsevier Inc. All rights reserved.

Citation

Ming Shi, Min-Hua Zheng, Zhi-Rong Liu, Ze-Lan Hu, Ying Huang, Jia-Yin Chen, Gang Zhao, Hua Han, Yu-Qiang Ding. DCC is specifically required for the survival of retinal ganglion and displaced amacrine cells in the developing mouse retina. Developmental biology. 2010 Dec 1;348(1):87-96