Signaling Pathways in Anterior-Posterior Patterning

Abstract

Tissues that give rise to head, trunk, and tail of a vertebrate body are patterned along the anterior-posterior (AP) axis long before the definitive structures are formed. How AP specification is achieved during embryogenesis is a fundamental question that has drawn the interest of generations of scientists. Several features of amphibians, especially Xenopus in recent decades, such as rapid development, accessibility to microsurgery throughout development, ease of evaluating AP tissue characteristics by both anatomical/histological and molecular landmarks, and availability of tools to manipulate gene expression and function, make them great animal models to interrogate the signaling pathways involved in AP patterning. Classical experimental embryologists explored tissue explants, conjugates, and transplants in their search for general principles for AP neural specification. Their results led to distinct models, the two most prominent ones proposing: (1) multiple region-specific inducers of AP neural characters; or (2) combinatorial actions of a general neural activator with a graded transforming agent at different AP positions. Modern molecular biologists identified key signaling pathways, such as retinoic acid (RA), fibroblast growth factor (FGF), and Wnt, as crucial regulators of posterior development. These signals, unlike inhibitors of the bone morphogenetic protein (BMP) pathway, do not normally induce neural markers but can promote posterior neural gene expression when combined with BMP antagonists. The molecular data thus support the notion of activation-transformation signals in AP patterning. However, a more complex story than the two-signal model seems to exist. This chapter aims to review several major findings made by both experimental embryology and molecular biology studies, discuss how the identified signals in neural induction and patterning help to revisit the classical models, and lay out a number of remaining issues that await further investigation.