Normal retinal development and retinofugal projections in mice lacking the retina-specific variant of actin-binding LIM domain protein.
The actin-binding LIM domain protein (abLIM) is the mammalian homologue of UNC-115, a protein mediating axon guidance in C. elegans. AbLIM is widely expressed with three isoforms differing from one another by the length of their amino termini. Experiments utilizing dominant-negative mutants in the chick retina suggested a role for abLIM in axon path finding in retinal ganglion cells (RGCs). To investigate which variant is involved in the regulation of mammalian RGC axon guidance, we analyzed their expression profile in mice. The longest variant, abLIM-L, is highly enriched in the ganglion cell layer. AbLIM-L is up-regulated postnatally which temporally overlaps with the period of RGC axon remodeling. In contrast, the abLIM-M and abLIM-S variants are widespread and remain relatively constant through development. By selective gene targeting, we ablated abLIM-L to explore its functional significance in vivo. AbLIM-L mutant mice exhibit no apparent morphological or functional defects in photoreceptors and inner retinal neurons. Retinofugal projections and synaptic maturation also appear normal. These data suggest that abLIM-M is likely the isoform performing the essential function related to axon guidance.
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Berman-Gund Laboratory for the Study of Retinal Degenerations and Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA.
Huang
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Ma
H F
HF
Gooley
J J
JJ
Aparacio
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J
Roof
D J
DJ
Chen
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C
Chen
D F
DF
Li
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T
D000818:Animals; D001369:Axons / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D060588:LIM Domain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D009434:Neural Pathways / Q000254:growth & development / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012160:Retina / Q000254:growth & development* / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
C107440:ABLIM1 protein, human; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D020033:Protein Isoforms