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PMID:16720875

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Citation

Veltmaat, JM, Relaix, F, Le, LT, Kratochwil, K, Sala, FG, van Veelen, W, Rice, R, Spencer-Dene, B, Mailleux, AA, Rice, DP, Thiery, JP and Bellusci, S (2006) Gli3-mediated somitic Fgf10 expression gradients are required for the induction and patterning of mammary epithelium along the embryonic axes. Development 133:2325-35

Abstract

Little is known about the regulation of cell fate decisions that lead to the formation of five pairs of mammary placodes in the surface ectoderm of the mouse embryo. We have previously shown that fibroblast growth factor 10 (FGF10) is required for the formation of mammary placodes 1, 2, 3 and 5. Here, we have found that Fgf10 is expressed only in the somites underlying placodes 2 and 3, in gradients across and within these somites. To test whether somitic FGF10 is required for the formation of these two placodes, we analyzed a number of mutants with different perturbations of somitic Fgf10 gradients for the presence of WNT signals and ectodermal multilayering, markers for mammary line and placode formation. The mammary line is displaced dorsally, and formation of placode 3 is impaired in Pax3ILZ/ILZ mutants, which do not form ventral somitic buds. Mammary line formation is impaired and placode 3 is absent in Gli3Xt-J/Xt-J and hypomorphic Fgf10 mutants, in which the somitic Fgf10 gradient is shortened dorsally and less overall Fgf10 is expressed, respectively. Recombinant FGF10 rescued mammogenesis in Fgf10(-/-) and Gli3Xt-J/Xt-J flanks. We correlate increasing levels of somitic FGF10 with progressive maturation of the surface ectoderm, and show that full expression of somitic Fgf10, co-regulated by GLI3, is required for the anteroposterior pattern in which the flank ectoderm acquires a mammary epithelial identity. We propose that the intra-somitic Fgf10 gradient, together with ventral elongation of the somites, determines the correct dorsoventral position of mammary epithelium along the flank.

Links

PubMed Online version:10.1242/dev.02394

Keywords

Animals; Body Patterning; Ectoderm/cytology; Ectoderm/physiology; Embryo, Mammalian/anatomy & histology; Embryo, Mammalian/physiology; Embryonic Induction; Embryonic Structures/cytology; Embryonic Structures/physiology; Epithelium/embryology; Epithelium/physiology; Female; Fibroblast Growth Factor 10/genetics; Fibroblast Growth Factor 10/metabolism; Gene Expression Regulation, Developmental; In Situ Hybridization; Kruppel-Like Transcription Factors/genetics; Kruppel-Like Transcription Factors/metabolism; Mammary Glands, Animal/anatomy & histology; Mammary Glands, Animal/embryology; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Signal Transduction/physiology; Somites/cytology; Somites/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PAX3

acts_upstream_of_or_within

GO:0060594: mammary gland specification

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2687297

P

Seeded From UniProt

complete

MOUSE:FGF10

acts_upstream_of_or_within

GO:0060595: fibroblast growth factor receptor signaling pathway involved in mammary gland specification

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1859647

P

Seeded From UniProt

complete

MOUSE:FGF10

acts_upstream_of_or_within

GO:0060595: fibroblast growth factor receptor signaling pathway involved in mammary gland specification

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FGF10

acts_upstream_of_or_within

GO:0060594: mammary gland specification

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95729

P

Seeded From UniProt

complete

MOUSE:FGF10

acts_upstream_of_or_within

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1859647

P

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0060594: mammary gland specification

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1099809

P

Seeded From UniProt

complete

MOUSE:FGFR2

acts_upstream_of_or_within

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2153811

P

Seeded From UniProt

complete

MOUSE:FGFR2

acts_upstream_of_or_within

GO:0060595: fibroblast growth factor receptor signaling pathway involved in mammary gland specification

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2153811

P

Seeded From UniProt

complete


See also

References

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