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First published online 23 February 2005
doi: 10.1242/dev.01735

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Genetics of shoulder girdle formation: roles of Tbx15 and aristaless-like genes

Sanne Kuijper¹, Annemiek Beverdam^1,*, Carla Kroon¹, Antje Brouwer¹, Sophie Candille², Gregory Barsh² and Frits Meijlink^1,

¹ Hubrecht Laboratory, The Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
² Departments of Genetics and Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

Author for correspondence (e-mail: frits{at}niob.knaw.nl)

Accepted 2 February 2005

The diverse cellular contributions to the skeletal elements of the vertebrate shoulder and pelvic girdles during embryonic development complicate the study of their patterning. Research in avian embryos has recently clarified part of the embryological basis of shoulder formation. Although dermomyotomal cells provide the progenitors of the scapular blade, local signals appear to have an essential guiding role in this process. These signals differ from those that are known to pattern the more distal appendicular skeleton. We have studied the impact of Tbx15, Gli3, Alx4 and related genes on formation of the skeletal elements of the mouse shoulder and pelvic girdles. We observed severe reduction of the scapula in double and triple mutants of these genes. Analyses of a range of complex genotypes revealed aspects of their genetic relationship, as well as functions that had been previously masked due to functional redundancy. Tbx15 and Gli3 appear to have synergistic functions in formation of the scapular blade. Scapular truncation in triple mutants of Tbx15, Alx4 and Cart1 indicates essential functions for Alx4 and Cart1 in the anterior part of the scapula, as opposed to Gli3 function being linked to the posterior part. Especially in Alx4/Cart1 mutants, the expression of markers such as Pax1, Pax3 and Scleraxis is altered prior to stages when anatomical aberrations are visible in the shoulder region. This suggests a disorganization of the proximal limb bud and adjacent flank mesoderm, and is likely to reflect the disruption of a mechanism providing positional cues to guide progenitor cells to their destination in the pectoral girdle.

Key words: Aristaless-like genes, Gli3, Mouse mutants, Pax genes, Scapula, Skeletogenesis, Tbx15

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