Sonic Hedgehog Mediates the Polarizing Activity of the ZPA

Retinoic Acid Synthesis and Signaling during Early Organogenesis

http://faculty.buffalostate.edu/eastondp/dpeastonbiolog/Bio%20601/pdf%20files/Harfe%20et%20al%20ZPA.pdf

Evidence for an Expansion-Based Temporal Shh Gradient in Specifying Vertebrate Digit Identities

ALL-trans retinoic acid (RA) is well known as a biologically active form of vitamin A and a teratogen1-8. The identification of nuclear receptors for this ligand9-11 suggests strongly that it is an endogenous signal molecule, and measurements of RA12 and teratogenic manipulations13-15 suggest further that RA is a mor-phogen specifying the anteroposterior axis during limb development. Besides the limb, RA and other retinoids affect development of other organs, including the central nervous system (CNS)4,6,7,16-18. None of these other effects has been investigated in detail. Our purpose here was to begin analysing the effects of RA on CNS development in Xenopus laevis. We find that RA acts on the developing CNS, transforming anterior neural tissue to a posterior neural specification. These and other19 findings raise the possibility that RA mediates an inductive interaction regulating anteroposterior differentiation within the CNS. Following recent reports implicating transforming growth factor-β2-like20,21 and fibroblast growth factor-like factors21,22 in mesoderm induction, this indicates that a different type of signal molecule (working through a nuclear receptor, not a plasma membrane receptor) might mediate inductive cell interactions during early embryonic development.

Retinoic acid causes an anteroposterior transformation in the developing central nervous system.

https://www.zora.uzh.ch/id/eprint/987/1/StrOrg93.pdf

Organizing activity of wingless protein in Drosophila.

The polarizing region, a small group of cells at the posterior margin of the limb bud, acts as a signalling region to specify the pattern of structures which develop across the anteroposterior axis of the limb1. When a polarizing region is grafted to the anterior margin of a second limb, a mirror-image symmetrical limb develops1,2. There is indirect evidence that the signal from the polarizing region is a diffusible morphogen3. In an attempt to identify the nature of the putative morphogen, we have developed a method whereby extracts of polarizing region cells and chemicals can be locally applied to the wing bud by being bound to implanted beads and other inert carriers. The chemicals tested included hyaluronidase, dibutyryl cyclic AMP and thalidomide. All experiments have been negative until, at the suggestion of Dr J. Pitts, we tested retinoic acid because of its effects on cell to cell communication and cell differentiation, and we have now for the first tune been able to mimic the action of the polarizing region with a defined chemical.

L. Wolpert

Papers

Local application of retinoic acid to the limb bond mimics the action of the polarizing region