Modulation of cell signal interpretation by primary cilium remodelling during vertebrate neuronal differentiation
Authors
Raman Das (1)
Affiliations
- University of Manchester
During vertebrate embryonic development, differentiating neurons undergo acute cessation of canonical, Gli transcription mediated Shh signalling through primary cilium disassembly, leading to cell cycle exit. Following this, newborn neurons reassemble a new, molecularly distinct primary cilium, a process we call primary cilium remodelling. This process corresponds with a switch in Shh signal interpretation from a canonical to non-canonical, Gli transcription independent mechanism which now directs neuron polarisation and axon extension in response to the ventral Shh gradient. The remodelled primary cilium is characterised by accumulation of the key Shh transducer Smoothened (Smo), and GPR161, a negative regulator of canonical Shh signalling. However, the precise mechanisms through which this unique ciliary configuration mediates the switch to non-canonical Shh interpretation to drive correct neuronal polarisation remain unclear. Using high-resolution live-tissue imaging in the chick neural tube, we show that Smo and GPR161 cooperate to drive axon extension. Here, high levels of GPR161 accumulation in the remodelled cilium lead to the switch to non-canonical Shh signalling through elevated ciliary cAMP levels. Overall, these results provide new insights into how cells can harness the molecular plasticity of the primary cilium to achieve context specific interpretation of extracellular signals.
References
Keywords
Live imaging, primary cilium, embryonic development, neuronal differentiation, signalling