Interaction of retinoic acid and scl controls primitive blood development

Abstract

Hematopoietic development during embryogenesis involves the interaction of extrinsic signaling pathways coupled to an intrinsic cell fate that is regulated by cell-specific transcription factors. Retinoic acid (RA) has been linked to stem cell self-renewal in adults and also participates in yolk sac blood island formation.

A DEAB-sensitive aldehyde dehydrogenase regulates hematopoietic stem and progenitor cells development during primitive hematopoiesis in zebrafish embryos

“…This had enabled us to address specifically the mechanism of action of aldh, independent of the ATRA effects on dorsoventral patterning and vascular formation, which was often seen at pharmacological doses. [24][25][26] Second, the present study has suggested a complex mode of regulation of primitive hematopoiesis by aldh. We performed extensive gene expression profiling and functional screening for all 15 known zebrafish aldh isoforms.…”

“…Very recently, de Jong et al 24 showed that DEAB treatment induced gata1 expression in wild type and partially rescued gata1 expression in the cdx4 mutant embryos. Remarkably, the rescue manifested only when the embryos were treated with DEAB between gastrulation and somitogenesis.…”

Erythroid‐extrinsic regulation of normal erythropoiesis by retinoic acid receptors

“…Due to the embryonic lethality of compound RAR mutant mice it has not been possible to define the requirement for RAR signalling in erythropoiesis. Several reports provided evidence for a possible contribution of retinoid signalling in primitive erythropoiesis and the expression of erythropoietin (Kambe et al, 2000;de Jong et al, 2010).…”

Genomic Strategies for Terminal Cell Fate Specification

“…A series of experiments is summarized in Fig. 5.4(A) using cdx4 mutants, RA and an RA signaling inhibitor, in which gata1 expression was monitored (de Jong et al, 2010). These perturbations show that RA indirectly inhibits expression of gata1 and blocks erythropoiesis, and that this effect can be rescued by forced expression of scl, a direct activator of gata1 expression.…”

“…5.3(A1), PLM) in the zebrafish embryo is established with respect to the anterior/posterior body axis downstream of expression of caudal genes (cdx4 and cdx1a). These cdx genes indirectly and redundantly affect primitive hematopoiesis in the posterior lateral mesoderm in two ways (Davidson and Zon, 2006;de Jong et al, 2010). Loss of cdx function (by mutation or morpholino treatment) precludes most primitive erythropoiesis.…”