1. Antagonistic and Cooperative Actions of Kif7 and Sufu Define Graded Intracellular Gli Activities in Hedgehog Signaling
- Author
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Chi-chung Hui, Shigeru Makino, Rong Mo, Kelvin King Lo Law, Xiaoyun Zhang, and Vijitha Puviindran
- Subjects
Mouse ,Cellular differentiation ,Regulator ,lcsh:Medicine ,Developmental Signaling ,Fluorescent Antibody Technique ,Kinesins ,Cell Fate Determination ,Mice ,Molecular Cell Biology ,Pattern Formation ,lcsh:Science ,In Situ Hybridization ,Genetics ,Mice, Knockout ,Multidisciplinary ,Microscopy, Confocal ,Cell Differentiation ,Animal Models ,Signaling in Selected Disciplines ,Hedgehog signaling pathway ,Cell biology ,Spinal Cord ,Signal transduction ,Intracellular ,Research Article ,Signal Transduction ,Blotting, Western ,Kruppel-Like Transcription Factors ,Cell fate determination ,Biology ,Signaling Pathways ,Zinc Finger Protein GLI1 ,Model Organisms ,GLI2 ,Animals ,Hedgehog Proteins ,Hedgehog ,Analysis of Variance ,lcsh:R ,Molecular Development ,Signaling ,Repressor Proteins ,lcsh:Q ,Gene Function ,Organism Development ,Animal Genetics ,Developmental Biology - Abstract
Graded Hedgehog (Hh) signaling governs the balance of Gli transcriptional activators and repressors to specify diverse ventral cell fates in the spinal cord. It remains unclear how distinct intracellular Gli activity is generated. Here, we demonstrate that Sufu acts universally as a negative regulator of Hh signaling, whereas Kif7 inhibits Gli activity in cooperation with, and independent of, Sufu. Together, they deter naive precursors from acquiring increasingly ventral identity. We show that Kif7 is also required to establish high intracellular Gli activity by antagonizing the Sufu-inhibition of Gli2. Strikingly, by abolishing the negative regulatory action of Sufu, diverse ventral cell fates can be specified in the absence of extracellular Hh signaling. These data suggest that Sufu is the primary regulator of graded Hh signaling and establish that the antagonistic and cooperative actions of Kif7 and Sufu are responsible for setting up distinct Gli activity in ventral cell fate specification.
- Published
- 2012