The Cerberus/Dan-family
protein Charon is a negative regulator of Nodal signaling during left-right
patterning in zebrafish
Hashimoto H, Rebagliati M, Ahmad N, Muraoka O, Kurokawa T, Hibi M and Suzuki
T
Development 131(8):1741-53 (2004)
SUMMARY
We have isolated a novel gene, charon, that encodes a member of the Cerberus/Dan
family of secreted factors. In zebrafish, Fugu and flounder, charon is
expressed in regions embracing Kupffer's vesicle, which is considered
to be the teleost fish equivalent to the region of the mouse definitive
node that is required for left-right (L/R) patterning. Misexpression of
Charon elicited phenotypes similar to those of mutant embryos defective
in Nodal signaling or embryos overexpressing Antivin(Atv)/Lefty1, an inhibitor
for Nodal and Activin. Charon also suppressed the dorsalizing activity
of all three of the known zebrafish Nodal-related proteins (Cyclops, Squint
and Southpaw), indicating that Charon can antagonize Nodal signaling.
Because Southpaw functions in the L/R patterning of lateral plate mesoderm
and the diencephalon, we asked whether Charon is involved in regulating
L/R asymmetry. Inhibition of Charon's function by antisense morpholino
oligonucleotides (MOs) led to a loss of L/R polarity, as evidenced by
bilateral expression of the left side-specific genes in the lateral plate
mesoderm (southpaw, cyclops, atv/lefty1, lefty2 and pitx2) and diencephalon
(cyclops, atv/lefty1 and pitx2), and defects in early (heart jogging)
and late (heart looping) asymmetric heart development, but did not disturb
the notochord development or the atv/lefty1-mediated midline barrier function.
MO-mediated inhibition of both Charon and Southpaw led to a reduction
in or loss of the expression of the left side-specific genes, suggesting
that Southpaw is epistatic to Charon in left-side formation. These data
indicate that antagonistic interactions between Charon and Nodal (Southpaw),
which take place in regions adjacent to Kupffer's vesicle, play an important
role in L/R patterning in zebrafish.
LINK
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