| Autor: |
Shariq S. Ansari, Miriam E. Dillard, Yan Zhang, Mary Ashley Austria, Naoko Boatwright, Elaine L. Shelton, Amanda Johnson, Brandon M. Young, Zoran Rankovic, John D. Schuetz, Camenzind G. Robinson, Stacey K. Ogden |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.05.06.490951 |
| Popis: |
Sonic Hedgehog (SHH) signaling is an essential driver of embryonic patterning that, when corrupted, leads to developmental disorders and cancers. SHH effector responses are organized through nonmotile primary cilia that grow and retract with the cell cycle and in response to distinct extracellular cues. Destabilization of primary cilium length corrupts SHH pathway regulation, which places significant pressure on SHH to maintain ciliary architecture. Herein, we investigate whether SHH signaling promotes ciliary length control. We reveal a signal crosstalk circuit induced by SHH activation of Phospholipase A2 (cPLA2) that drives ciliary EP4signaling to stabilize primary cilium length. We demonstrate that chemical or genetic blockade of SHH-EP4crosstalk leads to destabilized primary cilium cyclic AMP (cAMP) control, reduced ciliary length, and attenuated SHH pathway induction. Accordingly, we find thatEp-/-mice display shortened neuroepithelial primary cilia and altered SHH-dependent neuronal cell fate specification. Thus, SHH initiates a signaling crosstalk circuit that maintains primary cilium length for a robust downstream signaling response. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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