Retinoic acid induces polarizing activity but is unlikely to be a morphogen in the chick limb bud

The idea of morphogen gradients has long been an important one in developmental biology. Studies with amphibians and with Xenopus in particular have made significant contributions to demonstrating the existence, identity, and mechanisms of action of morphogens. Mesoderm induction and patterning by activin, nodals, bone morphogenetic proteins, and fibroblast growth factors have been analyzed thoroughly and reveal recurrent and combinatorial roles for these protein growth factor morphogens and their antagonists. The dynamics of nodal-type signaling and the intersection of VegT and ␤-catenin intracellular gradients reveal detailed steps in early long-range patterning. Interpretation of gradients requires sophisticated mechanisms for sharpening thresholds, and the activin-Xbra-Gsc system provides an example of this. The understanding of growth factor signal transduction has elucidated growth factor morphogen action and provided tools for dissecting their direct longrange action and distribution. The physical mechanisms of morphogen gradient establishment are the focus of new interest at both the experimental and theoretical level. General themes and emerging trends in morphogen gradient studies are discussed.

Section: Establishment Of Morphogen Gradients Part I: Evidence For Dmentioning

confidence: 99%

Morphogen gradients, positional information, and Xenopus: Interplay of theory and experiment

Green

2002

“…Early experiments indicated the presence of a gradient of RA in the chick limb bud (Thaller and Eichele, 1987) and showed that RA applied exogenously could mimic the zone of polarising activity (ZPA), indicting a role in patterning the anterior to posterior (thumb to little finger) axis of the developing limb (Summerbell, 1983;Tickle et al, 1982). It is now known that ectopic RA does this by inducing shh expression in the ZPA, and that Shh is the anterior posterior morphogen (Niederreither et al, 2002;Noji et al, 1991;Wanek et al, 1991). RA has also been proposed to control proximal to distal patterning of the limb via direct regulation of the proximally expressed Meis homeodomain proteins, Meis1 and Meis2 (Mercader et al, 2000(Mercader et al, , 2005.…”

Section: Introductionmentioning

confidence: 99%

Expression of key retinoic acid modulating genes suggests active regulation during development and regeneration of the amphibian limb

McEwan

Lynch

Beck

2011

We have previously shown differential regulation of components of the Retinoic acid (RA) pathway in Xenopus tadpole hindlimb regeneration. RA is thought to act as a morphogen, providing positional information during development and regeneration. We have investigated the regulation of genes involved in RA synthesis, catabolism, and binding in developing and regenerating Xenopus limbs. Our data indicate that RA is synthesised by Raldh2 in proximal cells during limb bud outgrowth. Furthermore, Cyp26b is expressed transiently in the progress zone of developing limbs and the blastema of regenerating limbs suggesting degradation of RA occurs in both processes. The RA‐binding protein Crabp2 is also upregulated during regeneration. We summarise this data to predict the presence of evolving gradients of RA in the developing amphibian limb. Thus, RA from the stump cells could be responsible for the establishment of proximal‐distal pattern during limb regeneration, as predicted by classical studies. Developmental Dynamics 240:1259–1270, 2011. © 2011 Wiley‐Liss, Inc.

“…High performance liquid chromatography (HPLC) analysis of dissected embryonic tissues, together with analysis of embryonic explants placed on RA-responsive reporter cell lines, have demonstrated that RA is present within specific embryonic tissues and at unequal levels (Maden et al, 1998, and references therein). There has been some debate as to whether RA may act as a morphogen, i.e., may be released in the form of concentration gradients across developing morphogenetic fields (e.g., in the limb bud; Thaller and Eichele, 1987;Noji et al, 1991). Recent work has provided evidence that a RA gradient is operating across the hindbrain field in the zebrafish embryo (White et al, 2007;White and Schilling, 2008).…”

Section: Introductionmentioning

confidence: 99%

Fate of retinoic acid–activated embryonic cell lineages

Dollé

Fraulob

Gallego-Llamas

et al. 2010

Retinoic acid (RA), a vitamin A derivative, is synthesized by specific cell populations and acts as a diffusible embryonic signal activating ligand‐inducible transcription factors, the RA receptors (RARs). RA‐activatable transgenic systems have revealed many discrete, transient sites of RA action during development. However, there has been no attempt to permanently label the RA‐activated cell lineages during mouse ontogenesis. We describe the characterization of a RA‐activatable Cre transgene, which through crosses with a conditional reporter strain (the ROSA26R lacZ reporter), leads to a stable labeling of the cell populations experiencing RA signaling during embryogenesis. RA response‐element (RARE) ‐driven Cre activity mimics at early stages the known activity of the corresponding RARE‐lacZ transgene (Rossant et al.,1991). Stable labeling of the Cre‐excised cell populations allows to trace the distribution of the RA‐activated cell lineages at later stages. These are described in relationship with current models of RA activity in various developmental systems, including the embryonic caudal region, limb buds, hindbrain, sensory organs, and heart. Developmental Dynamics 239:3260–3274, 2010. © 2010 Wiley‐Liss, Inc.