Disease relevance of Fgf15

• We demonstrate that Fgf15 expression within the pharyngeal arches is unaltered by a loss of Tbx1, a key regulator of pharyngeal arch development implicated in DiGeorge syndrome [1].
• Together with cardiac outflow tract defects in Fgf15 mutants, the conservation of enhancers in the hindbrain/spinal cord and pharyngeal epithelia suggests that human FGF19 (ortholog of Fgf15) is involved in early development and the distribution of cardiac neural crest cells and is one of the candidate genes for congenital heart defects [2].
• Fgf15 is expressed in the optic vesicle, a subset of progenitor cells of neural retina, and emerging ganglion and amacrine cells during retinogenesis [3].

High impact information on Fgf15

• We present evidence that Fgf15 shows Shh-dependent expression in the diencephalon and may participate in this interaction, at least in part, by regulating the ability of dorsal neural precursors to respond to dorsally secreted Wnt mitogens [4].
• The FGF-15 gene is expressed in a regionally restricted pattern in the developing nervous system, suggesting that FGF-15 may play an important role in regulating cell division and patterning within specific regions of the embryonic brain, spinal cord and sensory organs [5].
• Unlike Fgf19, Fgf15 is not expressed in mesoderm underlying the presumptive otic placode, but is expressed in the adjacent neurectoderm [6].
• Fibroblast growth factor 15 (Fgf15) is expressed in the developing mouse central nervous system and pharyngeal arches [2].
• Fgf15 mutant mice showed defects of the cardiac outflow tract probably because of aberrant behavior of the cardiac neural crest cells [2].

Associations of Fgf15 with chemical compounds

• Ostα(-/-)Fxr(-/-) mice exhibited decreased ileal FGF15 expression, restoration of intestinal cholesterol absorption, and increases in hepatic Cyp7a1 expression, fecal BA excretion, and BA pool size [7].

Biological context of Fgf15

• Study of Fgf15 gene expression in developing mouse brain [8].
• Luciferase assay showed that the 3.6-kb Fgf15 enhancer/promoter was activated by Gli2 [9].
• Fgf15 is required for proper morphogenesis of the mouse cardiac outflow tract [1].
• Moreover, over-expression of Fgf15 resulted in up-regulation of Fgf8 expression in the isthmus/r1 [2].
• Here, we describe the phenotype of mice lacking fibroblast growth factor 15 (Fgf15), which encodes a secreted signaling molecule expressed within the developing pharyngeal arches [1].

Anatomical context of Fgf15

• Fgf15 appeared early in the developing neural epithelium, in domains where Fgf8 gene is also expressed and, at later stages, in specific groups of neural cells [8].
• Fgf15 expression in the diencephalon/midbrain was greatly reduced in the seven-somite Shh mutant embryos [9].

Regulatory relationships of Fgf15

• In addition, the thalamic expression of Fgf15 has been recently reported under the control of Shh signalling gene, expressed in the diencephalic basal plate (Development 129 (2002) 4807) [8].

Other interactions of Fgf15

• Luciferase assays and transgenic analysis revealed that the Fgf15 gene is a direct target of Shh [10].
• Fgf15 expression is localized, like Fgf8, in secondary neural tube organizers: the isthmic organizer (IsO) and the anterior neural ridge (ANR) [8].
• The Fgf15 expression domain coincided with that of Gli1 and overlapped with that of Gli2 at this stage [9].
• This appears to result in a failure to establish an ectodermal signalling center expressing Fgf3 and Fgf15 [11].
• Here we analyze the expression of Fgf15 at different stages of mouse development in relation to Fgf8 and Otx2 expression patterns [12].

References