The extracellular matrix component WIF-1 is expressed during, and can modulate, retinal development.
We have shown previously that components of the extracellular matrix (ECM) modulate neuronal development. Here, we searched for additional ECM elements that might play roles in retinal histogenesis and identified a secreted glycoprotein that is heavily expressed in the retina. This molecule, named by others Wnt Inhibitory Factor-1 (WIF-1), is expressed during and after the period of rod photoreceptor morphogenesis in the mouse. We show that a potential WIF-1 ligand, Wnt4, as well as a potential Wnt4 receptor, fzd4, and a potential Wnt4 coreceptor, LRP6, are expressed in the region of, and at the time of, rod photoreceptor genesis. WIF-1 and Wnt4 are coexpressed during retinal development and bind to each other; therefore, they are likely to interact during rod production. WIF-1 protein inhibits rod production, and anti-WIF-1 antibodies increase rod production; in contrast, Wnt4 promotes rod production. Together, these data suggest that WIF-1 and Wnt4, both components of the ECM, regulate mammalian photoreceptor development.
Hunter
Dale D
DD
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA. dale.hunter@tufts.edu
Zhang
Minlei
M
Ferguson
Jill W
JW
Koch
Manuel
M
Brunken
William J
WJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011973:Receptors, LDL / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D051153:Wnt Proteins; D060528:Wnt4 Protein
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; C402930:FZD4 protein, human; D051157:Frizzled Receptors; C498581:Fzd4 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555476:Lrp6 protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011973:Receptors, LDL; D012097:Repressor Proteins; C555581:WNT4 protein, human; C118544:Wif1 protein, mouse; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse