Journal
DEVELOPMENTAL BIOLOGY
Volume 313, Issue 1, Pages 307-319Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2007.10.023
Keywords
neural induction; Xenopus laevis; gene regulation; neural induction; sox2; sox3; BMP; FGF; Vent
Categories
Funding
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM042341] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS048918] Funding Source: NIH RePORTER
- NIGMS NIH HHS [GM42341, R01 GM042341] Funding Source: Medline
- NINDS NIH HHS [NS048918, R01 NS048918, R01 NS048918-03] Funding Source: Medline
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The formation of the nervous system is initiated when ectodermal cells adopt the neural fate. Studies in Xenopus demonstrate that inhibition of BMP results in the formation of neural tissue. However, the molecular mechanism driving the expression of early neural genes in response to this inhibition is unknown. Moreover, controversy remains regarding the sufficiency of BMP inhibition for neural induction. To address these questions, we performed a detailed analysis of the regulation of the soxB1 gene, sox3, one of the earliest genes expressed in the neuroectoderm. Using ectodermal explant assays, we analyzed the role of BMP, Wnt and FGF signaling in the regulation of sox3 and the closely related soxB1 gene, sox2. Our results demonstrate that both sox3 and sox2 are induced in response to BMP antagonism, but by distinct mechanisms and that the activation of both genes is independent of FGF signaling. However, both require FGF for the maintenance of their expression. Finally, sox3 genomic elements were identified and characterized and an element required for BMP-mediated repression via Vent proteins was identified through the use of transgenesis and computational analysis. Interestingly, none of the elements required for sox3 expression were identified in the sox2 locus. Together our data indicate that two closely related genes have unique mechanisms of gene regulation at the onset of neural development. (c) 2007 Elsevier Inc. All rights reserved.
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