Retinoid signaling regulates primitive (yolk sac) hematopoiesis.
It is known from nutritional studies that vitamin A is an important factor for normal hematopoiesis, though it has been difficult to define its precise role. The vitamin A-deficient (VAD) quail embryo provides an effective ligand "knockout" model for investigating the function of retinoids during development. The VAD embryo develops with a significant reduction in erythroid cells, which has not been noted previously. Activation of the primitive erythroid program and early expression of the erythroid marker GATA-1 occurs, though GATA-1 levels eventually decline, consistent with the erythropoietic and hemoglobin deficits. However, from its early stages, the GATA-2 gene fails to be expressed normally in VAD embryos. The bone morphogenetic protein (BMP)-signaling pathway regulates GATA-2, and BMP4 expression becomes reduced in the caudal embryonic region of VAD embryos. Adding BMP4 to cultured VAD-derived explants rescues the production of erythroid cells, whereas normal embryos cultured in the presence of the BMP antagonist noggin are defective in primitive hematopoiesis. We find that cell clusters of primitive blood islands undergo an inappropriate program of apoptosis in the VAD embryo, which can explain the deficit in differentiated primitive blood cells. We propose that vitamin A-derived retinoids are required for normal yolk sac hematopoiesis and that an embryonic retinoid-BMP-GATA-2 signaling pathway controls progenitor cell survival relevant to primitive hematopoiesis.
Ghatpande
Satish
S
Department of Developmental and Molecular Biology, Chanin 501, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
Ghatpande
Ashwini
A
Sher
Justin
J
Zile
Maija H
MH
Evans
Todd
T
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D050989:GATA2 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006454:Hemoglobins / Q000032:analysis; D020287:In Situ Nick-End Labeling; D009024:Morphogenesis; D011784:Quail; D012097:Repressor Proteins / Q000235:genetics; D012176:Retinoids / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D015017:Yolk Sac / Q000187:drug effects / Q000502:physiology*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050989:GATA2 Transcription Factor; D006454:Hemoglobins; D012097:Repressor Proteins; D012176:Retinoids; D014157:Transcription Factors