Journal
DEVELOPMENTAL CELL
Volume 26, Issue 4, Pages 358-368Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2013.07.014
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Funding
- Tri-Institutional Starr Foundation
- New York State Stem Cell Science (NYSTEM)
- National Institutes of Health (NIH) [EY11307, EY016805]
- Research to Prevent Blindness (RPB)
- Tohoku University
- Grants-in-Aid for Scientific Research [23770136] Funding Source: KAKEN
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Primary cilia undergo cell-cycle-dependent assembly and disassembly. Emerging data suggest that ciliary resorption is a checkpoint for S phase reentry and that the activation of phospho(T94)Tctex-1 couples these two events. However, the environmental cues and molecular mechanisms that trigger these processes remain unknown. Here, we show that insulin-like growth-1 (IGF-1) accelerates G(1)-S progression by causing cilia to resorb. The mitogenic signals of IGF-1 are predominantly transduced through IGF-1 receptor (IGF-1R) on the cilia of fibroblasts and epithelial cells. At the base of the cilium, phosphorylated IGF-1R activates an AGS3-regulated G beta gamma signaling pathway that subsequently recruits phospho(T94)Tctex-1 to the transition zone. Perturbing any component of this pathway in cortical progenitors induces premature neuronal differentiation at the expense of proliferation. These data suggest that during corticogenesis, a cilium-transduced, noncanonical IGF-1R-G beta gamma-phospho(T94) Tctex-1 signaling pathway promotes the proliferation of neural progenitors through modulation of ciliary resorption and G(1) length.
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