1. Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California at San Francisco, San Francisco, California 94143-0452, USA
2. Present address: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA.

Correspondence to: Gail R. Martin Correspondence and requests for materials should be addressed to G.R.M. (e-mail: Email: gmartin@itsa.ucsf.edu).

Abstract

To determine the role of fibroblast growth factor (FGF) signalling from the apical ectodermal ridge (AER), we inactivated Fgf4 and Fgf8 in AER cells or their precursors at different stages of mouse limb development. We show that FGF4 and FGF8 regulate cell number in the nascent limb bud and are required for survival of cells located far from the AER. On the basis of the skeletal phenotypes observed, we conclude that these functions are essential to ensure that sufficient progenitor cells are available to form the normal complement of skeletal elements, and perhaps other limb tissues. In the complete absence of both FGF4 and FGF8 activities, limb development fails. We present a model to explain how the mutant phenotypes arise from FGF-mediated effects on limb bud size and cell survival.

1. Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California at San Francisco, San Francisco, California 94143-0452, USA
2. Present address: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA.

Correspondence to: Gail R. Martin Correspondence and requests for materials should be addressed to G.R.M. (e-mail: Email: gmartin@itsa.ucsf.edu).