Comparative analysis of genes downstream of the Hoxd cluster in developing digits and external genitalia.
Mammalian Hox genes encode transcription factors that are crucial for proper morphogenesis along the various body axes. Despite their extensive structural and functional characterization, the nature of their target genes remains elusive. We have addressed this question by using DNA microarrays to screen for genes whose expression in developing distal forelimbs and genital eminences was significantly modified in the absence of the full Hoxd gene complement. This comparative approach not only identified specific candidate genes, but also allowed the examination of whether a similar Hox expression pattern in distinct tissues leads to the modulation of the same or different downstream genes. We report here a set of potential target genes, most of which were not previously known to play a role in the early stages of either limb or genital bud development. Interestingly, we find that the majority of these candidate genes are differentially expressed in both structures, although often at different times. This supports the idea that both appendices involve similar genetic controls, both upstream and downstream of the Hox gene family. These results highlight the surprising mechanistic relationship between these rather different body parts and suggest a common developmental strategy to build up the most distal appendicular structures of the body, i.e. the digits and the penis/clitoris.
Cobb
John
J
National Research Center (NCCR Zoology and Animal Biology, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
Duboule
Denis
D
D000818:Animals; D005121:Extremities / Q000196:embryology*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005836:Genitalia, Female / Q000196:embryology*; D005837:Genitalia, Male / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D005810:Multigene Family; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D036121:Receptor, EphA3 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D000099184:Serum-Glucocorticoid Regulated Kinases
D018398:Homeodomain Proteins; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D036121:Receptor, EphA3; D014157:Transcription Factors; D000099184:Serum-Glucocorticoid Regulated Kinases; C094041:Hoxa11 protein, mouse; C113761:Tenm4 protein, mouse; C491717:Epha3 protein, mouse