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Presenting Author(s) Benoit Robert
Abstract Title Role of Msx genes in inductive signal transduction in the developing limb bud.
Full author List Yvan LALLEMAND, Marie-Anne NICOLA, Casto RAMOS, Antoine BACH, Benoît ROBERT
Text of abstract

Msx1 and Msx2 genes in vertebrates are expressed at many sites during embryogenesis that are places for induction between ectoderm and mesoderm, such as the apical region of the limb bud, facial processes, tooth buds, hair follicles, mammary primordia. Mutations of Msx1 and Msx2 have further demonstrated that these genes play a critical role in BMP2/BMP4 signal transduction in tooth bud and hair follicle, respectively. In addition, these genes are expressed at the dorsal midline of the neural tube. We have demonstrated that they are required at the diencephalon level for Wnt1 expression and maintenance of a functional midline.

In the limb, neither Msx1 nor Msx2 mutant exhibits an altered phenotype. In contrast, limbs from the double mutant are affected along the three axes. They are shorter and lack anterior cartilage elements. In situ analysis using several markers shows that no region with anterior identity ever forms, resulting in frequent oligodactyly. This is correlated with the absence of dorso-ventral boundary formation in the anterior ectoderm. Paradoxically, polydactyly is also frequent and appears to be associated with extended FGF activity in the apical ectodermal ridge (AER) and deregulation of Shh expression. Most of these defects may be linked to an impairment in AER formation and maintenance, with a deficiency in anterior AER formation at early stages and an extended maintenance of activity at later stages. The role this phenotype suggests for MSXs in BMP, FGF, SHH and WNT signalling along the three limb axes will be discussed.

Supported by grants from ARC and AFM.
Which session is your work most relevant to: Limb patterning