Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from outflow region at E9.5

ABSTRACT: A high concentration of maternal retinoic acid (RA), the active derivative of vitamin A, is well known as a teratogenic agent which can cause developmental defects. Our previous studies have shown that the maternal administration of RA to mice within a narrow developmental window induces outflow tract (OFT) septum defects, which closely resembles human transposition of the great arteries (TGA), although the responsible factors and pathogenic mechanisms of the TGA induced by RA still remain unknown. To identify the candidate genes involved in the altered development of the OFT in RA-induce TGA model, we isolated the RNA from E9.5 control and RA-treated OFT regions, and performed a microarray analysis. Approximately 200 outflow tract region were isolated from control and RA-treated embryos (embryonic day 9.5). We sought to obtain the candidate genes involved in the altered development of the OFT in RA-induce heart defects.

ORGANISM(S): Mus musculus

SUBMITTER: Masahide Sakabe

PROVIDER: E-GEOD-33472 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Retinoic acid (RA), the bioactive derivative of vitamin A, is essential for vertebrate heart development. Both excess and reduced RA signaling lead to cardiovascular malformations, particularly affecting the cardiac outflow tract (OFT). The cellular mechanisms underlying the effects of RA signaling during OFT morphogenesis are not fully understood. To address this question, we used transient maternal RA supplementation to rescue the early lethality resulting from inactivation of the murine retinaldehyde dehydrogenase 2 (Raldh2) gene. By embryonic day 13.5, Raldh2-/- hearts exhibited OFT septation defects. Although cardiac neural crest cells (cNCC) were present in OFT cushions of Raldh2-/- mutant embryos, we observed that cNCC were ectopically located in the peripheral region of the endocardial cushions, closer to the myocardium rather than immediately subjacent to the endocardium. Mislocated cNCC were aligned in parallel instead of perpendicular arrays to the endocardial surface within the proximal OFT. Supernumerary mesenchyme was generated both in and ex vivo within the cushions by Raldh2-/- mutant endocardium and found in place of the cNCC in a subendocardial, medial position. Although mislocated and misoriented, mutant cNCC resembled wildtype cells in their compaction density and individually elongated shape. Our data show that RA signaling acts on cNCC orientation relative to the septation plane and position within OFT cushions during septation process. Transcriptomic analysis and pathway-specific readout suggest that up-regulation of the Bmp pathway may be responsible for increased endothelial-to-mesenchymal transition, leading thereby to displacement of cNCC. E10.5 stage embryonic mouse outflow tracts were microdissected. Four pools of four outflow tracts were established for wildtype (WT) and mutant (Raldh2-/-) embryos derived from dams whose food had been supplemented with all-trans-RA (Sigma) directly mixed into powdered food at 0.1 mg/g food and offered between E7.5 and E8.5. Total RNA was extracted using Macherey-Nagel NucleoSpinÂ® RNA columns without on-column DNase digestion.

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Expression data from outflow region at E9.5

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