Wong TC , Rebbert M , Chen X , Heffer A , Zarelli VE , Dawid IB , Zhao H .

Z01 HD001002-26 Intramural NIH HHS

	Fig. 1. Transcriptome analysis of animal explants induced by co-injection of wnt3a and chd mRNA. (A) Schematic diagram of experimental procedures. (B) Kctd15 suppressed the expression of NC marker genes in animal cap assays. Both blastomeres of two-cell stage embryos were injected with the indicated mRNAs. RT-PCR was performed to examine expression of snai2, sox9, and foxd3. Co-overexpression of wnt3a and chd strongly induced the expression of these genes, and the induction was suppressed by addition of kctd15. Odc was the loading control. WE, whole embryos. (C,D) The top ten enriched GO terms in differentially expressed genes in the comparison of (B) induced to control (WC/L), and (C) induced/inhibited to induced (WCK/WC) animal caps.
	Fig. 2. Spatial expression pattern of ddcp1 encoding a Duf domain protein. (A-C) ddcp1 was expressed along the edge of neural plate. Notably, two stronger staining patches (arrows) were detected in whole mount embryos (A) and transverse sections (B). With the closure of neural tube, the two signaling patches merged and were located at the frontal region of the head (D-G). Ant, anterior view; lat, lateral view. Ac, archerteron; ev, eye vesicle; bv, brain vesicle; hb, hindbrain.
	Fig. 3. Spatial expression pattern of pdgfra and cfp. (A-B) Strong signals of pdgfra were detected in branchial arches at tail bud and tadpole stages. (C-E) Cfp signals were detected first at mid neurula stage, and appear as two stripes at the anterior neural plate indicated by red arrows (C). The signals were detected in brain, lens, and ear vesicle at tail bud and tadpole stages (D, E).
	Fig. 4. Spatial expression pattern of zswim5. Zswim5 was first detected at the dorsal blastopore lip in early gastrula (A,B), and then was preferentially expressed in the future neural plate at later gastrula stages (C). At early neurula stages, zswim5 signals were restricted at the anterior neural plate, partially covering the NC region (D-F). (G,H) Transverse section (G) and sagittal section (H) of stage15 embryos. Red arrows point to stained regions. At mid neurula stages, zswim5 signals were restricted in NC and anterior border of the neural plate (I,J). (K-R) Zswim5 expression at tail bud and tadpole stages. Zswim5 was mainly expressed in the anterior neural tube including forebrain, midbrain, hindbrain, and anterior portion of the spinal cord. In addition, signals were also detected in the retina of the developing eye and the forming cranial nerves (pointed by red arrows). N’ and P’ indicate the planes of the sections shown in N and P, respectively. Ac, archenteron; bt, blastocoel; ev, eye vesicle; eym, endodermal yolk mass; fg, foregut; hb, hindbrain; mb, midbrain; nt, notochord; rt, retina; and sc, spinal cord.
	Fig. 4. Spatial expression pattern of zswim5. Zswim5 was first detected at the dorsal blastopore lip in early gastrula (A,B), and then was preferentially expressed in the future neural plate at later gastrula stages (C). At early neurula stages, zswim5 signals were restricted at the anterior neural plate, partially covering the NC region (D-F). (G,H) Transverse section (G) and sagittal section (H) of stage15 embryos. Red arrows point to stained regions. At mid neurula stages, zswim5 signals were restricted in NC and anterior border of the neural plate (I,J). (K-R) Zswim5 expression at tail bud and tadpole stages. Zswim5 was mainly expressed in the anterior neural tube including forebrain, midbrain, hindbrain, and anterior portion of the spinal cord. In addition, signals were also detected in the retina of the developing eye and the forming cranial nerves (pointed by red arrows). N’ and P’ indicate the planes of the sections shown in N and P, respectively. Ac, archenteron; bt, blastocoel; ev, eye vesicle; eym, endodermal yolk mass; fg, foregut; hb, hindbrain; mb, midbrain; nt, notochord; rt, retina; and sc, spinal cord.
	Fig. 5. Spatial expression pattern of complement component C3 (C3). C3 signals were not detected by late gastrula stages (A). Its expression appeared at the anterior border of the neural plate, and then became restricted at the NC (B, C). NC expression was confirmed by sectioning (D). C3 expression in the NC declined quickly, and an expression domain gradually appeared at the ventral region of the trunk (E,F). Sections from stage 32 embryos indicated that C3 was expressed in the somatic and splanchnic layer of lateral plate mesoderm just internal to the epidermis. (G), sagittal section; (H), transversal section. Endodermal expression is prominent at later stages (I). Arrow points to an expression domain in the heart primordium. Ac, archenteron; bl, blood island; edy, endodermal yolk mass; ep, epidermis; lpm, lateral plate mesoderm; nc, neural crest; nt, neural tube; nd, notochord; sm, somite; vm, ventral mesoderm.
	Fig. 6. Overexpression of Kctd15 inhibits expression of zswim5 and C3. Both blastomeres of two-cell stage (A1,B1) or two dorsal blastomeres of four-cell stage embryos (A2,B2) were injected with kctd15 mRNA, and the injected embryos were collected at about stage 16. The expression zswim5 and C3 was strongly inhibited compared to those in control embryos (A,B). (A1) 72%, 13 of 18 embryos; (A2), 95%, 19 of 20 embryos; (B1), 58%, 11 of 17 embryos, and (B2) 73.7%, 14 of 19 embryos.
	loc496296 (hypothetical LOC496296) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 17, anterior view, dorsal up.
	loc496296 (hypothetical LOC496296) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	zswim4 (zinc finger SWIM-type containing 4) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 10, dorsal up.
	zswim4 (zinc finger SWIM-type containing 4) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 16, dorsal view, anterior up.

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