Segmental expression of Notch and Hairy genes in nephrogenesis.
Notch signaling pathway genes are required for nephrogenesis, raising the possibility that Notch effector Hairy-related genes should also control nephron formation. We performed in situ hybridization of Hairy transcription factors with segment-specific lectins and/or antibodies during early nephrogenesis to identify their possible roles in segment identity of the nephron. We found that among all of Notch downstream Hairy genes, only Hes1, Hes5, Hey1, and HeyL were expressed in a segment-specific manner in early nephrons and their expression pattern changed dynamically during metanephric development. Based on these patterns of expression, it was possible to propose a pairwise association of specific ligand and receptor and to suggest that the effector of this association is one of the Hairy transcription factors. We found that Hes5 is specifically expressed in the anlage of the loop of Henle, suggesting that it might be involved in the determination of its cell identity. We also examined the morphological appearance of kidneys from mice where the Hes1 or Hes5 genes were deleted and found that at least at the gross morphological level, there was little difference from wild-type kidneys. Because Hairy genes associate with other transcription factors to exert their effect, it is necessary to examine a more complete array of genetic deletions before a conclusion can be reached regarding their role in kidney development. These studies provide the basis for the future development of strategies to examine the role of individual effector molecules in the determination of the differentiation pattern of the nephron.
Chen
Linghong
L
Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 W 168th St., New York, NY 10032, USA.
Al-Awqati
Qais
Q
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D004848:Epithelium / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000196:embryology* / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C489734:Hes1 protein, mouse; C489685:Hes5 protein, mouse; C120420:Hey1 protein, mouse; C402588:Heyl protein, mouse; C064045:delta protein