Journal Article

Vertebrate limb bud development: moving towards integrative analysis of organogenesis

Zeller, Rolf, López-Ríos, Javier, Zuniga, Aimée

2009

Overview

Key Points Analyses of vertebrate limb bud development continue to provide fundamental insights into how vertebrate organogenesis is orchestrated. Classical patterning signals coordinate specification and determination with proliferation and survival. The underlying interactions define self-regulatory and robust signalling systems that interlink multiple pathways. A first integrative, data-driven model of limb organogenesis is presented, which should stimulate holistic and systems biology approaches for studying limb development and organogenesis more broadly. Vertebrate limb development is a classic developmental model. In this Review the authors discuss how existing models of this process might be integrated and might form a framework for a systems approach to understanding organogenesis. The limb bud is of paradigmatic value to understanding vertebrate organogenesis. Recent genetic analysis in mice has revealed the existence of a largely self-regulatory limb bud signalling system that involves many of the pathways that are known to regulate morphogenesis. These findings contrast with the prevailing view that the main limb bud axes develop largely independently of one another. In this Review, we discuss models of limb development and attempt to integrate the current knowledge of the signalling interactions that govern limb skeletal development into a systems model. The resulting integrative model provides insights into how the specification and proliferative expansion of the anteroposterior and proximodistal limb bud axes are coordinately controlled in time and space.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Agriculture / Animal Genetics and Genomics / Animals / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cell differentiation, maturation, development, hematopoiesis / Cell physiology / Classical studies / Extremities (Anatomy) / Feedback / Fundamental and applied biological sciences. Psychology / Gene Function / Genes / Genetic aspects / Genetics / Human Genetics / Humans / Limb Buds - embryology / Limb Buds - metabolism / Mice / Models, Biological / Molecular and cellular biology / Morphogenesis / Organogenesis / Physiological aspects / review-article / Signal Transduction