PROJECT SUMMARY/ABSTRACT
A major challenge in understanding how organs take shape is addressing how increases in morphological
complexity arise. Over the past half-century, our understanding of such symmetry-breaking has been
predominantly developed through molecular, genetic, and cellular frameworks. However, symmetry-breaking in
developing organs occurs at scales far larger than their individual molecular and cellular constituents, prompting
the question of how events at the molecular and cellular scale relate to the physical self-organization of organ
structure. To address this question, my lab centers its studies on the behavior of cell collectives, an understudied
nexus that serves as a mediator between subcellular processes and functionally relevant organ morphology. Our
prior work in considering collective cell, or supracellular, material properties has led to the hypothesis that the
role of key signals, known as morphogens, in sculpting organs is to influence cells and extracellular matrix such
that tissue material properties or “phase” are modulated. Thus, a key functional role of morphogens may be to
create diversity in supracellular mechanical behavior by fluidizing or solidifying tissue domains that result in the
increase of complexity in organ form. Here we will use a unique set of supracellular behavioral assays to
investigate new roles for signals in shaping emerging morphologies. We will first link where and when
morphogens are expressed in the forming follicle to the transcriptional profiles and multicellular architectures
that accompany morphogen activity (Aim 1). We will then leverage a constellation of novel collective cell
mechanics platforms to probe the functional consequence of morphogen activity at the supracellular scale. (Aim
2). Finally, through the integration of theory and experiment, we will explore the hypothesis that interacting
supracellular phases generate a mechanical instability in the skin that is sufficient to shape the organ (Aim 3).
Together these studies stand to highlight the need to consider supracellular properties necessary for tissue
symmetry breaking that are not reducible to the properties of individual cells. At the same time, our studies will
identify the molecular and cellular component parts that enable the diversification of emergent supracellular
material properties. Our investigations will pave the way for a generalizable paradigm for how morphogens can
create adjacent material phases within a single tissue, thereby generating the potential for mechanical self-
organization at the tissue scale. Finally, these studies will shed light on the multi-scale nature of organ formation
and serve as a foundation for future work aimed at addressing congenital defects, engineering stromal tissues
of specific material properties, and the rational channeling supracellular self-organizing potential in regenerative
medicine.