Distinct roles and regulations for HoxD genes in metanephric kidney development.
Hox genes encode homeodomain-containing proteins that control embryonic development in multiple contexts. Up to 30 Hox genes, distributed among all four clusters, are expressed during mammalian kidney morphogenesis, but functional redundancy between them has made a detailed functional account difficult to achieve. We have investigated the role of the HoxD cluster through comparative molecular embryological analysis of a set of mouse strains carrying targeted genomic rearrangements such as deletions, duplications, and inversions. This analysis allowed us to uncover and genetically dissect the complex role of the HoxD cluster. Regulation of metanephric mesenchyme-ureteric bud interactions and maintenance of structural integrity of tubular epithelia are differentially controlled by some Hoxd genes during renal development, consistent with their specific expression profiles. We also provide evidence for a kidney-specific form of colinearity that underlies the differential expression of two distinct sets of genes located on both sides and overlapping at the Hoxd9 locus. These insights further our knowledge of the genetic control of kidney morphogenesis and may contribute to understanding certain congenital kidney malformations, including polycystic kidney disease and renal hypoplasia.
Di-Poï
Nicolas
N
Department of Zoology and Animal Biology, University of Geneva, Geneva, Swizerland.
Zákány
József
J
Duboule
Denis
D
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D007668:Kidney / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D007763:Lac Operon; D008648:Mesoderm / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D007690:Polycystic Kidney Diseases / Q000196:embryology / Q000235:genetics / Q000473:pathology; D011247:Pregnancy; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014513:Ureter / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C489576:Hoxd8 protein, mouse; C490282:Hoxd9 protein, mouse; D009363:Neoplasm Proteins; D014157:Transcription Factors