Analysis of Fgf15 expression pattern in the mouse neural tube
Introduction
The dynamic process of neural tube regionalization in vertebrates is regulated by the combined expression of developmental genes [11]. Characteristic expression patterns of some genes have been found in transversal neuroepithelial domains that separate the main neural tube tagma (segments). These domains regulate local morphogenetic processes during brain development and are known as secondary organizers [8]. The molecular code present in each neuroepithelial organizer controls the generation of morphogenetic signals that induce and maintain regional characteristics in the surrounding neuroepithelium 4, 8. Three areas have been demonstrated as secondary organizers: the isthmic region (IsO) 8, 14, the zona limitans (ZLI) ([8], Echevarria et al., in preparation) and the anterior neural ridge (ANR) 5, 13.
The product of the Fgf8 gene is a secreted protein and was demonstrated to be the key molecule for the isthmic organizer activity 3, 7. This gene is also expressed in the other two organizer regions: the ZLI and the ANR 2, 8. Otx2 is a transcription factor related to the induction of the anterior part of neural plate and the specification of the IsO 1, 4, 10, 14. Fgf15 is a gene of the fibroblast growth factor family, which has been recently discovered in mouse embryos [9], and was proposed to be positively regulated by Otx2 expression [15].
In the present work we have carefully analyzed the expression of Fgf15 at different stages of the mouse embryo. Because the Fgf15 gene has been reported to be regulated by Otx2 expression and colocalizes in organizer regions with Fgf8, we have decided to explore the neural expression of Fgf15 in relation to Fgf8 and Otx2 expression patterns.
Section snippets
Mouse embryos
Mid-day of the day of the vaginal plug was considered as 0.5 day postcoitum in the timing of embryos. Staging of embryos used morphological criteria [6] . Timed pregnant Swiss mice were sacrificed and embryos dissected from decidual tissue in chilled phosphate-buffered saline 1× solution and fixed in 4% paraformaldehyde (PFA) at 4°C overnight. In addition to wholemount analysis, 125-μm-thick agarose gel vibratome sections were made for gene expression studies at several stages of development.
RNA probes
Results and discussion
We explored the expression of Fgf15 in the neural tube of mouse embryos from early neurulation stages (E8) to later stages of development (E15.5), when most of the neural regions are present and identifiable.
At E9.5 Fgf15 transcripts were detected at both sides of the IsO, showing a rostrocaudally decreasing gradient of expression in the alar plate of rhombomere 1, where the cerebellar plate is localized, and an inverse caudorostrally decreasing gradient in the mesencephalic alar plate, where
Acknowledgements
We are grateful to A. Simeone for the Fgf8 and Otx2 plasmids and A. McMahon for the Shh plasmid. L. Gimeno was supported by the Seneca Foundation Fellowship BP 00396/CV/00. This work has been supported by the Seneca Foundation 00708/CV/99.
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