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First published online May 23, 2006
doi: 10.1242/10.1242/dev.02394

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Gli3-mediated somitic Fgf10 expression gradients are required for the induction and patterning of mammary epithelium along the embryonic axes

Jacqueline M. Veltmaat^1,2,*, Frédéric Relaix³, Lendy T. Le¹, Klaus Kratochwil¹, Frédéric G. Sala^1,2, Wendy van Veelen^2,, Ritva Rice⁴, Bradley Spencer-Dene⁵, Arnaud A. Mailleux^2,, David P. Rice⁴, Jean Paul Thiery² and Saverio Bellusci^1,2

¹ The Saban Research Institute of Childrens Hospital Los Angeles/University of Southern California, Developmental Biology Program, Los Angeles, CA 90027, USA.
² Institut Curie/CNRS-UMR144, Equipe de Morphogenèse Cellulaire et Progression Tumorale, 75005 Paris, France.
³ Institut Pasteur/CNRS-URA 2578, Département de Biologie Moléculaire, Génétique Moléculaire du Développement, 75015 Paris, France.
⁴ King's College, Departments of Orthodontics and Craniofacial Development, London SE1 9RT, UK.
⁵ Cancer Research UK, London Research Institute, Experimental Pathology Laboratory, and Imperial College London, Department of Histopathology, London WC2A 3PX, UK.

^* Author for correspondence (e-mail: jveltmaat{at}chla.usc.edu and jmveltmaat{at}hotmail.com)

Accepted 4 April 2006

Little is known about the regulation of cell fate decisions that lead to the formation of five pairs of mammary placodes in the surface ectoderm of the mouse embryo. We have previously shown that fibroblast growth factor 10 (FGF10) is required for the formation of mammary placodes 1, 2, 3 and 5. Here, we have found that Fgf10 is expressed only in the somites underlying placodes 2 and 3, in gradients across and within these somites. To test whether somitic FGF10 is required for the formation of these two placodes, we analyzed a number of mutants with different perturbations of somitic Fgf10 gradients for the presence of WNT signals and ectodermal multilayering, markers for mammary line and placode formation. The mammary line is displaced dorsally, and formation of placode 3 is impaired in Pax3^ILZ/ILZ mutants, which do not form ventral somitic buds. Mammary line formation is impaired and placode 3 is absent in Gli3^Xt-J/Xt-J and hypomorphic Fgf10 mutants, in which the somitic Fgf10 gradient is shortened dorsally and less overall Fgf10 is expressed, respectively. Recombinant FGF10 rescued mammogenesis in Fgf10^-/- and Gli3^Xt-J/Xt-J flanks. We correlate increasing levels of somitic FGF10 with progressive maturation of the surface ectoderm, and show that full expression of somitic Fgf10, co-regulated by GLI3, is required for the anteroposterior pattern in which the flank ectoderm acquires a mammary epithelial identity. We propose that the intra-somitic Fgf10 gradient, together with ventral elongation of the somites, determines the correct dorsoventral position of mammary epithelium along the flank.

Key words: Ectodermal patterning, Mammary gland, Somites, Placode individuality, FGF10/FGFR2B, GLI3, PAX3, WNT signaling, Mouse

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Development 2006 133: e1205. [Full Text]  

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