Robson A et al. (2016), Expression of ribosomopathy genes during Xenopu...

XB-ART-52667

BMC Dev Biol 2016 Oct 26;161:38. doi: 10.1186/s12861-016-0138-5.

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Expression of ribosomopathy genes during Xenopus tropicalis embryogenesis.

Robson A , Owens ND , Baserga SJ , Khokha MK , Griffin JN .

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BACKGROUND: Because ribosomes are ubiquitously required for protein production, it was long assumed that any inherited defect in ribosome manufacture would be embryonically lethal. However, several human congenital diseases have been found to be associated with mutations in ribosome biogenesis factors. Surprisingly, despite the global requirement for ribosomes, these "ribosomopathies" are characterized by distinct and tissue specific phenotypes. The reasons for such tissue proclivity in ribosomopathies remain mysterious but may include differential expression of ribosome biogenesis factors in distinct tissues. METHODS: Here we use in situ hybridization of labeled antisense mRNA probes and ultra high temporal resolution RNA-Seq data to examine and compare expression of 13 disease associated ribosome biogenesis factors at six key stages in Xenopus tropicalis development. RESULTS: Rather than being ubiquitously expressed during development, mRNAs of all examined ribosome biogenesis factors were highly enriched in specific tissues, including the cranial neural crest and ventral blood islands. Interestingly, expression of ribosome biogenesis factors demonstrates clear differences in timing, transcript number and tissue localization. CONCLUSION: Ribosome biogenesis factor expression is more spatiotemporally regulated during embryonic development than previously expected and correlates closely with many of the common ribosomopathy phenotypes. Our findings provide information on the dynamic use of ribosome production machinery components during development and advance our understanding of their roles in disease.

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Species referenced: Xenopus tropicalis
Genes referenced: rbm28 rpl15 rpl26 rpl35a rpl38 rps14 rps17 rps19 rps29 rps7 sbds tcof1 utp4

???displayArticle.disOnts??? Bowen-Conradi syndrome [+]
???displayArticle.omims??? DIAMOND-BLACKFAN ANEMIA 1; DBA1 [+]

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	Fig. 1 a Schematic of ribosome biogenesis. The rDNA is transcribed by RNA polymerase I and the resulting rRNA is processed in the nucleolus before being incorporated into the large ribosomal subunit (LSU) or small ribosomal subunit (SSU). b Schematic of X. tropicalis embryos at examined stages. Major anatomical features are labeled. A: anterior, P: posterior, D: dorsal, R: ventral
	Fig. 2 Expression of disease-linked ribosome biogenesis factors in X. tropicalis embryos. a Expression of all four genes was detected in the 4-cell and gastrulating embryo. Signal was strongly detected in the neural folds at stage 16 and in the migrating neural crest at stage 22. b At later stages expression of all factors was detected in the facial primordia and developing brain. Note the restricted expression at the mid–hindbrain border and forebrain. Expression was also typically detected in ventral mesoderm and hypaxial muscle precursor cells. utp4 mRNA was strongly detected at the site of the future liver. c Red lines labeled a, b and c* in diagrams of stage 10 and 28 embryos represent the planes of section shown in a and b
	Fig. 3 rps genes are dynamically expressed in development. a Expression of all five rps genes examined was observed in the stage 10 gastrula, stage 16 neural folds, and migrating CNC at stage 20–22. b Each gene was widely detected in the developing head at later stages (28–40), including all the pharyngeal arches, brain, eyes and ears. rps17, 19 and 29 were also robustly detected in the ventral mesoderm, while rps7 was particularly defined in somites. With the exception of rps7, transcripts of all mRNAs were detected in the dorso-lateral plate mesodermal region where the pronephros and hypaxial muscle will form. c Red lines labeled a, b and c* in diagrams of stage 10 and 28 embryos represent the planes of section shown in a and b
	Fig. 4 Expression of rpl genes. a rpl mRNA was weakly detected or absent at early stages of development but, with the exception of rpl15, became up-regulated in the neural folds and migratory neural crest from neurula stages onwards. b At later stages expression of all four rpl genes was evident broadly throughout the head, pharyngeal arches, neural tube and ventral mesoderm/blood islands. c Red lines labeled a, b and c* in diagrams of stage 10 and 28 embryos represent the planes of section shown in a and b
	Fig. 5 Dynamics of gene expression of poly(A) + mRNA in transcripts per embryo . a Plot of all examined genes. Note the relatively consistent dynamics but variably levels of of RP gene transcription. b Expression dynamics of ribosome biogenesis factors. While variable, three pronounced peaks in expression are evident during development (red arrows). c Expression of individual biogenesis factors
	rbm28 (RNA binding motif protein 28) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	rpl15 (ribosomal protein L15) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	rpl26 (ribosomal protein L26) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	rpl35a (ribosomal protein L35a) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	rpl38 (ribosomal protein L38) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	rps7 (ribosomal protein S7) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	rps14 (ribosomal protein S14) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	rps17 (ribosomal protein S17) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	rps19(ribosomal protein S19) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	rps29 (ribosomal protein S29) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	sbds (Shwachman-Bodian-Diamond syndrome) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	tcof1 (Treacher Collins-Franceschetti syndrome 1) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	utp4 (UTP4 small subunit processome component) gene expression in Xenopus tropicalis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anterior left, dorsal up.
	Additional file 2: Comparison of digoxigenin labeled anti-sense and sense mRNA probes for each ribosomopathy gene in stage 16 embryos. Dorsal and anterior views are shown. Note the strong expression detected in the neural plate by the anti-sense mRNA probes while the control sense probed embryos remains unstained. (JPG 922 kb)