Requirements for efficient cell-type proportioning: regulatory timescales, stochasticity and lateral inhibition.

Abstract:

:The proper functioning of multicellular organisms requires the robust establishment of precise proportions between distinct cell types. This developmental differentiation process typically involves intracellular regulatory and stochastic mechanisms to generate cell-fate diversity as well as intercellular signaling mechanisms to coordinate cell-fate decisions at tissue level. We thus surmise that key insights about the developmental regulation of cell-type proportion can be captured by the modeling study of clustering dynamics in population of inhibitory-coupled noisy bistable systems. This general class of dynamical system is shown to exhibit a very stable two-cluster state, but also metastability, collective oscillations or noise-induced state hopping, which can prevent from timely and reliably reaching a robust and well-proportioned clustered state. To circumvent these obstacles or to avoid fine-tuning, we highlight a general strategy based on dual-time positive feedback loops, such as mediated through transcriptional versus epigenetic mechanisms, which improves proportion regulation by coordinating early and flexible lineage priming with late and firm commitment. This result sheds new light on the respective and cooperative roles of multiple regulatory feedback, stochasticity and lateral inhibition in developmental dynamics.

journal_name

Phys Biol

journal_title

Physical biology

authors

Pfeuty B,Kaneko K

doi

10.1088/1478-3975/13/2/026007

subject

Has Abstract

pub_date

2016-05-11 00:00:00

pages

026007

issue

2

eissn

1478-3967

issn

1478-3975

journal_volume

13

pub_type

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