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Retinoid signaling is required to complete the vertebrate cardiac left/right asymmetry pathway.
- Source :
-
Developmental biology [Dev Biol] 2000 Jul 15; Vol. 223 (2), pp. 323-38. - Publication Year :
- 2000
-
Abstract
- Vitamin A-deficient (VAD) quail embryos have severe abnormalities, including a high incidence of reversed cardiac situs. Using this model we examined in vivo the physiological function of vitamin A in the left/right (L/R) cardiac asymmetry pathway. Molecular analysis reveals the expression of early asymmetry genes activin receptor IIa, sonic hedgehog, Caronte, Lefty-1, and Fgf8 to be unaffected by the lack of retinoids, while expression of the downstream genes nodal-related, snail-related (cSnR), and Pitx2 is altered. In VAD embryos nodal expression in left lateral plate mesoderm (LPM) is severely downregulated and the expression domain altered during neurulation. Similarly, the expression of cSnR in the right LPM and of Pitx2 in the left side posterior heart-forming region (HFR) is downregulated in the VAD embryos. The lack of retinoids does not cause randomization or ectopic expression of nodal, cSnR, or Pitx2. At the six- to eight-somite stage nodal is expressed transiently in the left posterior HFR of normal quail embryos; this expression is missing in VAD embryos and may be linked to the loss of Pitx2 expression in this region of VAD quail embryos. Administration of retinoids to VAD embryos prior to the six-somite stage rescues the expression of nodal, cSnR, and Pitx2 as well as the randomized VAD cardiac phenotype. There is an absolute requirement for retinoids at the four- to five-somite developmental window for cardiogenesis and cardiac L/R specification to proceed normally. We conclude that retinoids do not regulate the left/right-specific sidedness assignments for expression of genes on the vertebrate cardiac asymmetry pathway, but are required during neurulation for the maintenance of adequate levels of their expression and for the development of the posterior heart tube and a loopable heart. Cardiac asymmetry may be but one of several critical events regulated by retinoid signaling in the retinoid-sensitive developmental window.<br /> (Copyright 2000 Academic Press.)
- Subjects :
- Activin Receptors, Type II
Animals
DNA-Binding Proteins isolation & purification
Fibroblast Growth Factor 8
Fibroblast Growth Factors isolation & purification
Heart Defects, Congenital etiology
Hedgehog Proteins
Homeodomain Proteins isolation & purification
Left-Right Determination Factors
Nodal Protein
Paired Box Transcription Factors
Proteins isolation & purification
Quail
Receptors, Growth Factor isolation & purification
Signal Transduction
Somites
Tissue Distribution
Transcription Factors isolation & purification
Transforming Growth Factor beta isolation & purification
Vitamin A Deficiency
Homeobox Protein PITX2
Avian Proteins
Body Patterning
Heart embryology
Nuclear Proteins
Retinoids metabolism
Trans-Activators
Vitamin A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0012-1606
- Volume :
- 223
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Developmental biology
- Publication Type :
- Academic Journal
- Accession number :
- 10882519
- Full Text :
- https://doi.org/10.1006/dbio.2000.9754