title: A polarised population of dynamic microtubules mediates homeostatic length control in animal cells.
abstract: Because physical form and function are intimately linked, mechanisms that maintain cell shape and size within strict limits are likely to be important for a wide variety of biological processes. However, while intrinsic controls have been found to contribute to the relatively well-defined shape of bacteria and yeast cells, the extent to which individual cells from a multicellular animal control their plastic form remains unclear. Here, using micropatterned lines to limit cell extension to one dimension, we show that cells spread to a characteristic steady-state length that is independent of cell size, pattern width, and cortical actin. Instead, homeostatic length control on lines depends on a population of dynamic microtubules that lead during cell extension, and that are aligned along the long cell axis as the result of interactions of microtubule plus ends with the lateral cell cortex. Similarly, during the development of the zebrafish neural tube, elongated neuroepithelial cells maintain a relatively well-defined length that is independent of cell size but dependent upon oriented microtubules. A simple, quantitative model of cellular extension driven by microtubules recapitulates cell elongation on lines, the steady-state distribution of microtubules, and cell length homeostasis, and predicts the effects of microtubule inhibitors on cell length. Together this experimental and theoretical analysis suggests that microtubule dynamics impose unexpected limits on cell geometry that enable cells to regulate their length. Since cells are the building blocks and architects of tissue morphogenesis, such intrinsically defined limits may be important for development and homeostasis in multicellular organisms.
authors.affiliation: Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, London, United Kingdom.
authors.forename: Remigio
authors.initials: R
authors.lastname: Picone
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Ren
authors.forename: Kenzo D
authors.initials: KD
authors.lastname: Ivanovitch
authors.forename: Jon D W
authors.initials: JD
authors.lastname: Clarke
authors.forename: Rachel A
authors.initials: RA
authors.lastname: McKendry
authors.forename: Buzz
authors.initials: B
authors.lastname: Baum
mesh_terms: D000818:Animals; D016764:Cell Polarity; D048429:Cell Size; D004330:Drosophila; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D008870:Microtubules / Q000502:physiology*