csal1 is controlled by a combination of FGF and Wnt signals in developing limb buds.
While some of the signaling molecules that govern establishment of the limb axis have been characterized, little is known about the downstream effector genes that interpret these signals. In Drosophila, the spalt gene is involved in cell fate determination and pattern formation in different tissues. We have cloned a chick homologue of Drosophila spalt, which we have termed csal1, and this study focuses on the regulation of csal1 expression in the limb bud. csal1 is expressed in limb buds from HH 17 to 26, in both the apical ectodermal ridge and the distal mesenchyme. Signals from the apical ridge are essential for csal1 expression, while the dorsal ectoderm is required for csal1 expression at a distance from the ridge. Our data indicate that both FGF and Wnt signals are required for the regulation of csal1 expression in the limb. Mutations in the human homologue of csal1, termed Hsal1/SALL1, result in a condition known as Townes-Brocks syndrome (TBS), which is characterized by preaxial polydactyly. The developmental expression of csal1 together with the digit phenotype in TBS patients suggests that csal1 may play a role in some aspects of distal patterning.
Farrell
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Department of Anatomy and Physiology, Division of Cell and Developmental Biology, University of Dundee, Wellcome Trust Biocenter, Dow Street, Dundee, DD1 5EH, United Kingdom.
Münsterberg
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D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002642:Chick Embryo; D003001:Cloning, Molecular; D004330:Drosophila; D029721:Drosophila Proteins; D004475:Ectoderm / Q000502:physiology; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018878:Limb Buds / Q000502:physiology*; D008934:Mitogens / Q000502:physiology; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins; D014981:Xenopus; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D016335:Zinc Fingers
D029721:Drosophila Proteins; C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D008934:Mitogens; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C103405:sal1-A protein, Xenopus; C085793:salm protein, Drosophila; C484468:spalt protein, vertebrate; D005346:Fibroblast Growth Factors