Ricerc@Sapienza

Data obtained by studying mammalian cells in absence of gravity strongly support the notion that cell
fate specification cannot be understood according to the current molecular model. A paradigmatic case in
point is provided by studying cell populations growing in absence of gravity. When the physical
constraint (gravity) is ‘experimentally removed’, cells spontaneously allocate into two morphologically
different phenotypes. Such phenomenon is likely enacted by the intrinsic stochasticity, which, in turn, is
successively ‘canalized’ by a specific gene regulatory network. Both phenotypes are thermodynamically
and functionally ‘compatibles’ with the new, modified environment. However, when the two cell subsets
are reseeded into the 1g gravity field the two phenotypes collapse into one. Gravity constraints the
system in adopting only one phenotype, not by selecting a pre-existing configuration, but more precisely
shaping it de-novo through the modification of the cytoskeleton three-dimensional structure. Overall,
those findings highlight how macro-scale features are irreducible to lower-scale explanations. The
identification of macroscale control parameters e as those depending on the field (gravity, electromagnetic
fields) or emerging from the cooperativity among the field's components (tissue stiffness, cellto-
cell connectivity) e are mandatory for assessing boundary conditions for models at lower scales, thus
providing a concrete instantiation of top-down effects.