Mouse FGF15 is the ortholog of human
and chick FGF19, but is not uniquely required for otic induction
Wright T J, Ladher R, McWhirter J, Murre C, Schoenwolf G C and Mansour
S L
Dev Biol 269(1):264-75 (2004)
SUMMARY
The inner ear develops from an ectodermal placode that is specified by
inductive signals from the adjacent neurectoderm and underlying mesoderm.
In chick, fibroblast growth factor (Fgf)-19 is expressed in mesoderm underlying
the presumptive otic placode, and human FGF19 induces expression of otic
markers in a tissue explant containing neural plate and surface ectoderm.
We show here that mouse Fgf15 is the sequence homolog of chick and human
Fgf19/FGF19. In addition, we show that FGF15, like FGF19, is sufficient
to induce expression of otic markers in a chick explant assay, suggesting
that these FGFs are orthologs. Mouse embryos lacking Fgf15, however, do
not have otic abnormalities at E9.5-E10.5, suggesting that Fgf15 is not
uniquely required for otic induction or early patterning of the otocyst.
To compare FGF15 and FGF19 signaling components and assess where signals
potentially redundant with FGF15 might function, we determined the expression
patterns of Fgf15 and Fgf19. Unlike Fgf19, Fgf15 is not expressed in mesoderm
underlying the presumptive otic placode, but is expressed in the adjacent
neurectoderm. Fgfr4, which encodes the likely receptor for both FGF19
and FGF15, is expressed in the neurectoderm of both species, and is also
expressed in the mesoderm only in chick. These results suggest the hypotheses
that during otic induction, FGF19 signals in either an autocrine fashion
to the mesoderm or a paracrine fashion to the neurectoderm, whereas FGF15
signals in an autocrine fashion to the neurectoderm. Thus, the FGFs that
signal to the neurectoderm are the best potential candidates for redundancy
with FGF15 during mouse otic development.
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