DCC is specifically required for the survival of retinal ganglion and displaced amacrine cells in the developing mouse retina.
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.
Shi
Ming
M
Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, China.
Zheng
Min-Hua
MH
Liu
Zhi-Rong
ZR
Hu
Ze-Lan
ZL
Huang
Ying
Y
Chen
Jia-Yin
JY
Zhao
Gang
G
Han
Hua
H
Ding
Yu-Qiang
YQ
D025042:Amacrine Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002470:Cell Survival; D000075389:DCC Receptor; D005124:Eye Abnormalities / Q000235:genetics / Q000473:pathology; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D016163:Genes, DCC; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000075389:DCC Receptor; C501910:Dcc protein, mouse; D005136:Eye Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins