TY - JOUR
T1 - Primary cilium remodelling mediates a cell signalling switch in differentiating neurons
AU - Toro-Tapia, Gabriela
AU - Das, Raman
PY - 2020/5/20
Y1 - 2020/5/20
N2 - Cellular differentiation leads to formation of specialised cell types and complex morphological variations. Often, differentiating cells transition states by switching how they respond to the signalling environment. However, the mechanisms regulating these transitions are poorly understood. Differentiating neurons delaminate from the neuroepithelium through the regulated process of apical abscission, which mediates an acute loss of polarity and primary cilium dis-assembly. Using high-resolution live-cell imaging in chick neural tube, we show that these cells retain an Arl13b+ particle which elongates and initiates intraflagellar trafficking (IFT) as it transits towards the cell body, indicating primary cilium remodelling. Strikingly, disrupting cilia during and after remodelling inhibits axon extension and leads to dramatic axon collapse respectively. Furthermore, cilium remodelling corresponds to a switch from a canonical to non-canonical cellular response to Shh. This work transforms our understanding of how cells can rapidly re-interpret signals to produce qualitatively different responses within the same tissue context.
AB - Cellular differentiation leads to formation of specialised cell types and complex morphological variations. Often, differentiating cells transition states by switching how they respond to the signalling environment. However, the mechanisms regulating these transitions are poorly understood. Differentiating neurons delaminate from the neuroepithelium through the regulated process of apical abscission, which mediates an acute loss of polarity and primary cilium dis-assembly. Using high-resolution live-cell imaging in chick neural tube, we show that these cells retain an Arl13b+ particle which elongates and initiates intraflagellar trafficking (IFT) as it transits towards the cell body, indicating primary cilium remodelling. Strikingly, disrupting cilia during and after remodelling inhibits axon extension and leads to dramatic axon collapse respectively. Furthermore, cilium remodelling corresponds to a switch from a canonical to non-canonical cellular response to Shh. This work transforms our understanding of how cells can rapidly re-interpret signals to produce qualitatively different responses within the same tissue context.
U2 - 10.1126/sciadv.abb0601
DO - 10.1126/sciadv.abb0601
M3 - Article
SN - 2375-2548
VL - 6
JO - Science Advances
JF - Science Advances
IS - 21
ER -