Pax-6 regulates expression of SFRP-2 and Wnt-7b in the developing CNS.
Wnt signaling regulates a wide range of developmental processes such as proliferation, cell migration, axon guidance, and cell fate determination. In this report, we studied the expression of secreted frizzled related protein-2 (SFRP-2), which codes for a putative Wnt inhibitor, in the developing nervous system. SFRP-2 is expressed in several discrete neuroepithelial domains, including the diencephalon, the insertion of the eminentia thalami into the caudal telencephalon, and the pallial-subpallial boundary (PSB). We also noted that Wnt-7b expression was similar to SFRP-2 expression. Because many of these structures are disrupted in Pax-6 mutant mice, we examined SFRP-2 and Wnt-7b expression in the forebrains of Pax-6 Sey/Sey mice. We found that Pax-6 mutants lack SFRP-2 expression in the PSB and diencephalon. Interestingly, Pax-6 mutants also lack Wnt-7b expression in the PSB, but Wnt-7b expression in the diencephalon is preserved. Furthermore, in the spinal cord of Pax-6 mutants, SFRP-2 and Wnt-7b expression was greatly reduced. Our results suggest that by virtue of its apposition to Wnt-7b expression, SFRP-2 may modulate its function, particularly at boundaries such as the PSB, and that changes in Wnt signaling contribute to the phenotype of Pax-6 mutants.
Kim
A S
AS
Neurodevelopmental Disorders Laboratory, Department of Neurology, University of California, San Francisco, California 94143, USA.
Anderson
S A
SA
Rubenstein
J L
JL
Lowenstein
D H
DH
Pleasure
S J
SJ
D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D006023:Glycoproteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017403:In Situ Hybridization; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009928:Organ Specificity; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors; D051153:Wnt Proteins; D000094742:Secreted Frizzled-Related Proteins
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; C088334:Distal-less homeobox proteins; C000605730:PAX6 protein, human; C000605732:Pax6 protein, mouse; C491628:Sfrp2 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C093661:Tes protein, mouse; C490675:WNT7B protein, human; C095937:Wnt7b protein, mouse