Retinoic acid-mediated patterning of the pre-pancreatic endoderm in Xenopus operates via direct and indirect mechanisms

Abstract

Early patterning of the endoderm as a prerequisite for pancreas specification involves retinoic acid (RA) as a critical signalling molecule in gastrula stage Xenopus embryos. In extension of our previous studies, we made systematic use of early embryonic endodermal and mesodermal explants. We find RA to be sufficient to induce pancreas-specific gene expression in dorsal but not ventral endoderm. The differential expression of retinoic acid receptors (RARs) in gastrula stage endoderm is important for the distinct responsiveness of dorsal versus ventral explants. Furthermore, BMP signalling, that is repressed dorsally, prevents the formation of pancreatic precursor cells in the ventral endoderm of gastrula stage Xenopus embryos. An additional requirement for mesoderm suggests the production of one or more further pancreas inducing signals by this tissue. Finally, recombination of manipulated early embryonic explants, and also inhibition of RA activity in whole embryos, reveal that RA signalling, as it is relevant for pancreas development, operates simultaneously on both mesodermal and endodermal germ layers.

In vitro organogenesis from undifferentiated cells in Xenopus

“…In addition, zebrafish and Xenopus embryos treated with exogenous RA showed enlargement of the pancreas, as well as enlargement of the liver in zebrafish, in the anterior direction (Stafford and Prince, 2002;Chen et al, 2004;Stafford et al, 2004). A recent study reported that RA is sufficient to induce pancreas-specific gene expression in the dorsal but not the ventral endoderm (Pan et al, 2007). Mouse embryos deficient for the RA-synthesizing enzyme retinaldehyde dehydrogenase 2 (RALDH2), if rescued from early lethality by maternal RA, lack active RA signaling in the foregut region.…”

Pancreas organogenesis: From bud to plexus to gland

“…In these organisms, RA from the overlying mesoderm posteriorizes the gut endoderm and promotes pancreasorgan allocation during gastrulation. Blocking RA signaling inhibits pancreas specification suggesting that RA is essential in this process Prince 2002, Kumar et al, 2003;Chen et al, 2004b;Stafford et al, 2004Stafford et al, , 2006Pan et al, 2007;Bayha et al, 2009). Based on the distribution of in vivo RA receptors (RAR) and results of cell-transplantation assays, it was concluded that RA acts directly on the endoderm for pancreas specification in zebrafish (Stafford et al, 2006).…”

Retinoic acid signaling in development: Tissue‐specific functions and evolutionary origins

“…In addition, localized endodermal expression of different rar paralogs further fine-tunes this RA signaling activity along the AP axis of the developing endoderm (Bertrand et al, 2007;Mollard et al, 2000). Finally, localized expression of rars in dorsal and ventral areas of the vertebrate endoderm may even create differential RA signaling activities along the dorsoventral (DV) body axis (Pan et al, 2007). To understand how and when these complex patterns of RA signaling activity evolved in the endoderm, it will be crucial to study in much greater detail the functions of RA in the endoderm of different invertebrate systems.…”