Caudalization by the amphibian organizer: brachyury, convergent extension and retinoic acid
Authors: Yamada Tuneo 
Published: April 2021

ABSTRACT
Caudalization, which is proposed to be one of two functions of the amphibian organizer, initiates posterior pathways of neural development in the dorsalized ectoderm. In the absence of caudalization, dorsalized ectoderm only expresses the most anterior (archencephalic) differentiation. In the presence of caudalization, dorsalized ectoderm develops various levels of posterior neural tissues, depending on the extent of caudalization. A series of induction experiments have shown that caudalization is mediated by convergent extension: cell motility that is based on directed cell intercalation, and is essential for the morphogenesis of posterior axial tissues.
During amphibian development, convergent extension is first expressed all-over the mesoderm and, after mesoderm involution, it becomes localized to the posterior mid-dorsal mesoderm, which produces notochord. This expression pattern of specific down regulation of convergent extension is also followed by the expression of the brachyury homolog. Furthermore, mouse brachyury has been implicated in the regulation of tissue elongation on the one hand, and in the control of posterior differentiation on the other. These observations suggest that protein encoded by the brachyury homolog controls the expression of convergent extension in the mesoderm. The idea is fully corroborated by a genetic study of mouse brachyury, which demonstrates that the gene product produces elongation of the posterior embryonic axis. However, there exists evidence for the induction of posterior dorsal mesodermal tissues, if brachyury homolog protein is expressed in the ectoderm. In both cases the brachyury homolog contributes to caudalization.
A number of other genes appear to be involved in caudalization. The most important of these is pintavallis, which contains a fork-head DNA binding domain. It is first expressed in the marginal zone. After mesoderm involution, it is present not only in the presumptive notochord, but also in the floor plate. This is in contrast to the brachyury homolog, whose expression is restricted to mesoderm.
The morphogenetic effects of exogenous RA on antero-posterior specification during amphibian embryogenesis are reviewed. The agent inhibits archencephalic differentiation and enhances differentiation of deuterencephalic and trunk levels. Thus the effect of exogenous RA on morphogenesis of CNS is very similar to that of caudalization, which is proposed to occur through the normal action of the organizer.
According to a detailed analysis of the effect of lithium on morphogenesis induced by the Cynops organizer, lithium has a caudalizing effect closely comparable with that of RA. Furthermore, lithium induces convergent extension in the prechordal plate, which normally does not show cell motility. This raises the question of whether the caudalizing effect of RA may be also dependent on CE which RA may induce in the treated tissue.
A number of chick embryonic tissues are known to show polarizing activity for limb development. All these tissues are known to express, or expected to express CE. This strongly suggests that these tissues induce CE in limb mesenchyme, and CE functions as the polarizing activity. Recently RA was shown to have a positive effect in this respect. This supports our proposal that RA induces CE in treated tissues.
According to the expanded model of dorsalization-caudalization, anteroposterior specification in mesoderm and ectoderm is the combined effect of dorsalization and caudalization:while dorsalization occurs at all AP levels, caudalization is limited to posterior of the anteroposterior border-line. In agreement with this, genes involved in dorsalization become expressed at all anteroposterior levels, while the main caudalizing gene is expressed behind the anteroposterior border-line at the stage CNS is induced.
The study of the neural inducing effects of noggin protein on competent ectoderm indicates that it is able to cause ectodermal dorsalization. In the absence of mesoderm, noggin protein induces only neural tissues with the anterior markers. But in the presence of mesoderm, noggin protein can induce neural tissues with the posterior markers. These results are in full agreement with the model of dorsalization-caudalization.