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Proc Natl Acad Sci U S A
2000 May 09;9710:5291-6. doi: 10.1073/pnas.090020497.
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Xenopus kielin: A dorsalizing factor containing multiple chordin-type repeats secreted from the embryonic midline.
Matsui M
,
Mizuseki K
,
Nakatani J
,
Nakanishi S
,
Sasai Y
.
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The midline tissues are important inductive centers of early vertebrate embryos. By signal peptide selection screening, we isolated a secreted factor, Kielin, which contains multiple cys-rich repeats similar to those in chordin (Chd). Expression of Kielin starts at midgastrula stages in the notochord and is detected in the floor plate of neurula embryos. Kielin is induced in mesoderm and in ectoderm by nodal-related genes. Chd is sufficient to activate Kielin expression in mesoderm whereas Shh or HNF-3beta in addition to Chd is required for induction in ectoderm. Kielin has a distinct biological activity from that of Chd. Injection of Kielin mRNA causes dorsalization of ventral marginal zone explants and expansion of MyoD expression in neurula embryos. Unlike Chd, Kielin does not efficiently induce neural differentiation of animal cap ectoderm, suggesting that the activity of Kielin is not simply caused by BMP4 blockade. Kielin is a signaling molecule that mediates inductive activities of the embryonic midline.
Figure 2 Whole-mount in situ hybridization analysis of Kielin expression in embryos at stage 10.5 (A; vegetal view), stage 12 (B; dorsal view), stage 14 (C; dorsal view), stage 19 (D; cleared dorsal view), stage 24 (E, cleared lateral view), and stage 28 (F, cleared lateral view). Histological analyses show Kielin expression in the axial mesoderm of a late gastrula (G), in the notochord and presumptive floor plate of a midneurula (H), and in the floor-plate region of an early tailbudembryo (I). Arrowheads, stomodeal-hypophyseal anlage; am, axial mesoderm; ect, ectoderm; ae, archenteron; fp, presumptive floor plate; s, somite; nt, notochord.
Figure 5 Overexpression of Kielin expands the MyoD expression region in vivo. Two left vegetal blastomeres of eight-cell embryos were injected with frame-shift Kielin (control) mRNA (600 pg; A, C, and E) and wild-type Kielin (KLN) mRNA (600 pg; B, D, and F). The injected embryos were harvested at stage 16 (A and B), stage 13 (C and D), or stage 19 (E and F) and analyzed by whole-mount in situ hybridization with a MyoD probe (A and B), a Xnot probe (C and D), or a NCAM probe (E and F).
Fig. 2. Kcp expression at stg. 24
Fig. 3. Regulation of Kielin expression in the marginal zone explant. VMZ
explants were prepared from embryos injected with control lacZ mRNA (300
pg; A), Chd mRNA (100 pg; B), Xnr-4 mRNA (200 pg; C), goosecoid mRNA (50
pg; D), HNF-3b mRNA (100 pg; E), and Xnot mRNA (300 pg; F). The explants
were prepared at stage 10.5, harvested at stage 12.5, and analyzed by in situ
hybridization with a Kielin probe.
Fig. 4. Regulation of Kielin expression in the animal cap ectoderm. Animal
caps were explanted at stage 10.5 from embryos injected with control mRNA
(1 ng; A and B), Chd mRNA (100 pg; C and D), Shh mRNA (900 pg; E and F), Chd
and Shh mRNAs (G and H), HNF-3b mRNA (50 pg; I and J), Chd and HNF-3b
mRNAs (K and L), cyc mRNA (200 pg; M and N), and Xnr4 mRNA (200 pg; O and
P). The explants were harvested at stage 20 and analyzed with a Kielin (KLN)
probe (A, C, E, G, I, K, M, and O) or harvested at stage 12 and hybridized with
a Xbra probe (B, D, F, H, J, L, N, and P).
Fig. 6. Kielin has a mesoderm-dorsalizing activity in VMZ assays, but does not
induce neural differentiation in the animal cap. VMZ explants were prepared
from embryos injected with control frame-shift Kielin (control) mRNA (300 pg;
A, D, G, and J), wild-type Kielin (KLN) mRNA (300 pg; B, E, H, and K), and Chd
mRNA (100 pg; C, F, I, and L). As Kilein mRNA is three times larger in size than
Chd mRNA, the injected mounts of mRNAs are similar in terms of molar ratio.
(A–I) VMZ assays. The VMZ explants harvested at stage 13 were analyzed by in
situ hybridization with a MyoD probe (A–C), Xnot probe (D–F), or a HNF-3b
probe (G–I). (J–L) Animal cap assays. Animal caps were explanted at stage 10.25
from embryos injected with control frame-shift Kielin mRNA (J), wild-type
Kielin mRNA (K), and Chd mRNA (L). The animal cap explants were harvested
at stage 20 and hybridized with a NCAM probe.
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