Suzuki A et al. (2017), Genomic organization and modulation of gene exp...

XB-ART-52580

Dev Biol 2017 Jun 15;4262:336-359. doi: 10.1016/j.ydbio.2016.09.016.

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Genomic organization and modulation of gene expression of the TGF-β and FGF pathways in the allotetraploid frog Xenopus laevis.

Suzuki A , Yoshida H , van Heeringen SJ , Takebayashi-Suzuki K , Veenstra GJC , Taira M .

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Inductive interactions mediated by the TGF-β and FGF-MAPK pathways are essential for specification of the germ layers and embryonic body axes during early vertebrate embryogenesis. TGF-β and FGF ligands signal through receptor Ser/Thr and Tyr kinases, respectively, and these signaling pathways cross-talk to regulate transcription and cell behavior. The allotetraploid Xenopus laevis and its ancestral diploid Xenopus tropicalis are versatile model organisms with which to study the inductive interactions and mechanisms of these signal transduction pathways. Here we have analyzed the draft genome of X. laevis with respect to the genomic organization and differential expression of genes in the TGF-β and FGF pathways. Genomic structure and gene expression analyses of pathway components in X. laevis revealed that genetic modulations, including deletions resulting in singletons and differential expression of homeologs, have occurred frequently among extracellular regulatory factors of the TGF-β pathway after allotetraploidization. Moreover, differential gene expression was found for factors regulating various cellular responses including co-receptors, decoy receptors, and intracellular negative regulators in both the TGF-β and FGF-MAPK pathways. We summarize the patterns of genetic alterations in the allotetraploid frog X. laevis and discuss the importance of these changes with regard to developmental processes.

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Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: chrd chrd.2 crebbp fmn1 gdf11.2 grem1 hck ltbp4 mapk1 tll2

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	Fig. 1. Overview of genomic structure and gene expression in the TGF-Î² pathway. L and S indicate homeologs on the L and S chromosomes, respectively. The suffixes e, p, and d following L or S indicate â€œexpansionâ€, â€œpseudogeneâ€, and â€œdeletionâ€, respectively. In cases where the genomic sequence was not available due to the absence of a scaffold or a large N gap, the L and S homeologs are indicated by the suffixes â€œns (no scaffold)â€ or â€œnn (no model due to N)â€. The expression of gdf11 and tll2 homeologs was not compared owing to the uncertainty of gene identity. Inequality signs indicate the relative expression between a homeologous pair of genes. Differentially expressed genes and singletons are shown as black and grey boxes, respectively.
	Fig. 2. Differential expression of nine TGF-Î² ligands (Aâ€“I). The y axis shows the TPM value from RNA-seq analysis. Gene expression of the L and S homeologs is indicated by the red and blue lines, respectively. oo12, oo34, and oo56 indicate oocyte stages 1/2, 3/4, and 5/6, respectively. The embryonic stages of Nieuwkoop and Faber (1967) are also indicated.
	Fig. 3. Differential expression of 17 extracellular regulatory factors (Aâ€“Q). The y axis shows the TPM value from RNA-seq analysis. Gene expression of the L and S homeologs is indicated by the red and blue lines, respectively. oo12, oo34, and oo56 indicate oocyte stages 1/2, 3/4, and 5/6, respectively. The embryonic stages of Nieuwkoop and Faber (1967) are also indicated.
	Fig. 4. Genomic structure of the chordin, gremlin1, formin1 and ltbp4 loci. (A) Genomic structure of the chordin loci. The chordin (chrd) gene is specifically amplified on the X. laevis L chromosome (chrd.e1.L and chrd.e2.L). (B) Epigenetic modifications of the X. laevis chordin loci. Shown are the genomic profiles of H3K4me3 (green), p300 (yellow), H3K36me3 (blue) and RNA Polymerase II (purple) ChIP-seq tracks. The gene annotation tracks show the chordin genes on the homeologous L (top) and S (bottom) chromosomes. The conservation between the L and S genomic sequence is shown in grey lines between the gene annotation tracks. (C) Genomic structure of the gremlin1 (grem1) and formin1 (fmn1) loci. Gremlin1 and Formin1 function to inhibit BMP signaling during limb formation. Both grem1 and fmn1 genes have been lost from the X. laevis S chromosome. (D) Genomic structure of the ltbp4 loci. The ltbp4 gene has been lost from the X. laevis S chromosome.
	Fig. 5. Differential expression of six receptors, co-receptors and receptor-associated intracellular factors in the TGF-Î² pathway (Aâ€“F). The y axis shows the TPM value from RNA-seq analysis. Gene expression of the L and S homeologs is indicated by the red and blue lines, respectively. oo12, oo34, and oo56 indicate oocyte stages 1/2, 3/4, and 5/6, respectively. The embryonic stages of Nieuwkoop and Faber (1967) are also indicated.
	Fig. 6. Overview of genomic structure and gene expression in the FGF pathway. L and S indicate homeologs on the L and S chromosomes, respectively. The suffixes e, p, and d following L or S indicate âexpansionâ, âpseudogeneâ, and âdeletionâ, respectively. In cases where the genomic sequence was not available due to the absence of a scaffold or a large N gap, the L and S homeologs are indicated by the suffixes âns (no scaffold)â or ânn (no model due to N)â. Inequality signs indicate the relative expression between a homeologous pair of genes. Differentially expressed genes and singletons are shown as black and grey boxes, respectively.
	Fig. 7. Differential expression of twelve FGF ligands, receptors, and components of the Rasâ€“MAPK pathway (A-L). The y axis shows the TPM value from RNA-seq analysis. Gene expression of the L and S homeologs is indicated by the red and blue lines, respectively. oo12, oo34, and oo56 indicate oocyte stages 1/2, 3/4, and 5/6, respectively. The embryonic stages of Nieuwkoop and Faber (1967) are also indicated.
	Fig. 8. Genomic structure of the hck loci. On the S chromosome, hck.S is largely deleted and becoming a pseudogene. In X. tropicalis, this locus is broken into scaffold790 containing hck gene and scaffold284.