Journal
DEVELOPMENTAL BIOLOGY
Volume 285, Issue 2, Pages 533-544Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2005.06.017
Keywords
limb development; Alx4; Gli3; antero-posterior patterning; gene regulation; sonic hedgehog; FGF4; polydactyly
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The role of the aristaless-related homeobox gene Alx4 in antero-posterior (AP-) patterning of the developing vertebrate limb has remained somewhat elusive. Polydactyly of Alx4 mutant mice is known to be accompanied by ectopic anterior expression of genes like Shh, Fgf4 and 5'Hoxd. We reported previously that polydactyly in Alx4 mutant mice requires SHH signaling, but we now show that in early Alx4(-/-) limb buds the anterior ectopic expression of Fgf4 and Hoxd13, and therefore disruption of AP-patteming, occurs independently of SHH signaling. To better understand how Alx4 functions in the pathways that regulate AP-patteming, we also studied genomic regulatory sequences that are capable of directing expression of a reporter gene in a pattern corresponding to endogenous AM expression in anterior limb bud mesenchyme. We observed, as expected for authentic Alx4 expression, expansion of reporter construct expression in a Shh(-/-) background. Total lack of reporter expression in a Gli3(-/-) background confirms the existence of GO-dependent and -independent AM expression in the limb bud. Apparently, these two modules of Alx4 expression are linked to dissimilar functions. (c) 2005 Elsevier Inc. All rights reserved.
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