Cellular signalling protrusions enable dynamic distant contacts in spinal cord neurogenesis
Posted on: 15 November 2024
Preprint posted on 12 October 2024
Notching it up a bit: distant cells can receive Notch signalling through cellular protrusions in the developing spinal cord.
Selected by Ankita WalvekarCategories: cell biology, developmental biology
Background
The Notch signalling pathway is a known cell communication pathway, occurring between neighbouring cells. The current preprint addresses the question of how Notch signalling could actually affect cells that are not direct neighbours. The authors postulate a mathematical model in which there are micro clusters of cells that periodically signal to (and beyond) adjacent cells. Previous experimental work showed the existence of such micro clusters (3-5 cells) and the oscillatory expression of the Notch target HES5 in these cells (Biga et al., 2021).
Because Notch signalling requires direct membrane contact for its activation, the preprint authors looked into the importance of membrane protrusions (like cytonemes) in allowing long-range signalling. These protrusions were already shown to be important for other signalling pathways like Shh and Wnt in the neural tube (Hall et al., 2024). Hence, the authors scored for the presence of cellular protrusions when micro clusters of HES5-expressing cells were present.
Main findings
- In this preprint the authors tested for and subsequently confirmed the presence of actin-based cell protrusions in radial glial cells in the mouse developing spinal cord, in fixed as well as live tissue samples.
- Additionally, they confirmed the presence of the Notch ligand DLL1 in these membrane protrusions.
- The authors further confirmed that the actin regulator CDC42 is involved in the formation of these protrusions.
- They show that perturbing the density of these protrusions caused reduced HES5 spatial periods, but this does not affect the length of the protrusions.
Why I highlight this preprint
I chose to highlight this preprint as I closely study signalling in the neural tube and was fascinated to know that Notch signalling could also be elicited through cell protrusions (apart from Shh and Wnt signalling) in the developing neural tube.
Questions to the authors
- Perturbing the formation of cellular protrusions affects DLL1, but how does it affect neural tube development? Does it cause any significant temporally-regulated developmental perturbations or is it inconsequential in the larger scheme of development?
- Would you expect any differences in the reception of Notch signalling through these protrusions in dorsal versus ventral neural tube cells?
- Do the cellular protrusions affect the other Notch signalling components, as HES5 is only one of the downstream targets?
References:
Biga, V., Hawley, J., Soto, X., Johns, E., Han, D., Bennett, H., Adamson, A.D., Kursawe, J., Glendinning, P., Manning, C.S. and Papalopulu, N. (2021) ‘A dynamic, spatially periodic, micro‐pattern of HES5 underlies neurogenesis in the mouse spinal cord’, Molecular Systems Biology, 17(5), pp. 1–27. Available at: https://doi.org/10.15252/msb.20209902.
Hall, E.T., Dillard, M.E., Cleverdon, E.R., Zhang, Y., Daly, C.A., Ansari, S.S., Wakefield, R., Stewart, D.P., Pruett-Miller, S.M., Lavado, A., Carisey, A.F., Johnson, A., Wang, Y.D., Selner, E., Tanes, M., Ryu, Y.S., Robinson, C.G., Steinberg, J. and Ogden, S.K. (2024) ‘Cytoneme signaling provides essential contributions to mammalian tissue patterning’, Cell, 187(2), pp. 276-293.e23. Available at: https://doi.org/10.1016/j.cell.2023.12.003.
doi: https://doi.org/10.1242/prelights.38890
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