Abstract:
:Splotch mice, which harbour mutations in the Pax3 gene, exhibit neural crest-related abnormalities including pigmentation defects, reduced or absent dorsal root ganglia and failure of cardiac outflow tract septation in homozygotes. Although splotch neural crest cells fail to colonise target tissues, they initiate migration in vivo and appear to migrate as well as wild type neural crest cells in vitro, suggesting that the neural crest abnormality in splotch may reside not in the neural crest cells themselves, but rather in the extracellular environment through which they migrate. We have examined the expression of genes encoding extracellular matrix molecules in Sp2H homozygous embryos and find a marked over-expression of transcripts for the chondroitin sulphate proteoglycan versican in the pathways of neural crest cell migration. Use of cadherin-6 expression as a marker for neural crest demonstrates a striking correlation between up-regulation of versican expression and absence of migrating neural crest cells, both in the mesenchyme lateral to the neural tube and in the lower branchial arches of Sp2H homozygotes. Pax3 and versican have mutually exclusive expression patterns in normal embryos whereas, in Sp2H homozygotes, versican is generally over-expressed with 'infilling' in regions that would normally express functional Pax3. Versican, like other chondroitin sulphate proteoglycans, is non-permissive for migration of neural crest cells in vitro, and we suggest that over-expression of this molecule leads to the arrest of neural crest cell migration in splotch embryos. Pax3 may serve to negatively regulate versican expression during normal development, thereby guiding neural crest cells into their pathways of migration.
journal_name
Mech Devjournal_title
Mechanisms of developmentauthors
Henderson DJ,Ybot-Gonzalez P,Copp AJdoi
10.1016/s0925-4773(97)00151-2subject
Has Abstractpub_date
1997-12-01 00:00:00pages
39-51issue
1-2eissn
0925-4773issn
1872-6356pii
S0925-4773(97)00151-2journal_volume
69pub_type
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journal_title:Mechanisms of development
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journal_title:Mechanisms of development
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pub_type: 杂志文章
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更新日期:2005-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:2004-12-01 00:00:00
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journal_title:Mechanisms of development
pub_type: 杂志文章
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journal_title:Mechanisms of development
pub_type: 杂志文章
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