Dataset Information

Cardiac Outflow tract septation defects in a DiGeorge syndrome model respond to Minoxidil treatment

ABSTRACT: Cardiac Outflow tract septation defects in a DiGeorge syndrome model respond to Minoxidil treatment

PROVIDER: PRJNA1085754 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	SRR28275254.fastq.gz	Fastqsanger.gz
	SRR28275255.fastq.gz	Fastqsanger.gz
	SRR28275256.fastq.gz	Fastqsanger.gz
	SRR28275257.fastq.gz	Fastqsanger.gz
	SRR28275258.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

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.

Dataset Information

Cardiac Outflow tract septation defects in a DiGeorge syndrome model respond to Minoxidil treatment

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets