Investigating the Supracellular Processes Underlying Emergent Material Phase Properties During Embryonic Skin Morphogenesis

Author

Karl H. Palmquist

Date of Award

2024

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Abstract

During embryonic development, vertebrate tissues are sculpted by the coordinated behaviors of cells.Vertebrate organs are complex, typically requiring the orchestrated dynamics of hundreds to thousands of cells. Yet, due to their functional significance, the mechanisms underlying organ formation are robust.This implies the need for mechanisms to constrain critical processes during embryogenesis. While much of developmental biology has focused on the aspects of self-organization that relate to patterns of chemicals and molecules across a tissue and their relationship to gene regulatory networks, less attention has been given to the physical mechanisms at play. In particular,it is poorly understood how, in complex tissues, cells self-organize in a robust manner. This line of inquiry has been expounded recently in a classic system for studying periodic pattern formation: the embryonic chicken skin. The formation of feather follicle primordia was shown to be mechanically driven by the developing dermis. Cellular pulling forces, balanced by tissue stiffness, generate periodically spaced multicellular aggregates of dermal progenitors. As the aggregates form, they compress epidermal cells, triggering molecular changes that initiate the feather follicle primordium gene expression program. Yet, two questions remained. How do cells coordinate and tune their mechanical forces across a field of cells in order to generate the correct pattern? Once the dermal condensate forms, what role do molecular signals from the epidermis have in three-dimensionally sculpting the feather follicle primordium? This thesis addresses these questions by examining tissue morphogenesis through the lens of regulatory processes that occur at the multicellular length scale. In Chapter Two, we develop an assay to reconstitute the initiation of follicle patterning ex vivo. We show that contractile cells rearrange and align the extracellular matrix (ECM). Reciprocal interactions between the cells and ECM, mediated by calcium signaling, progressively align the cell-ECM layer. This exchange transforms a mechanically unlinked collective of dermal cells into a continuum with coherent, long-range order. Combining theory with experiment, we show that this ordered cell-ECM layer behaves as an active contractile fluid that spontaneously forms regular patterns. In Chapter Three, we examine how molecular signals—BMPs and FGFs—enable transformation from a flat dermal condensate to a feather follicle primordium with three-dimensional architecture. By analyzing cellular and molecular patterns as the feather follicle primordium forms and matures, we show that distinct multicellular domains emerge during budding that spatially correlate with BMP and FGF activity. By reconstituting these BMP and FGF domains ex vivo, we show that FGF promotes solidification whereas BMP retains fluidity but enhances contractility. Furthermore, we show that a biphasic supracellular complex is sufficient to drive tissue budding, resulting in symmetry breaking in a new spatial dimension. Together, these results present a paradigm for how supracellular-scale material properties generate robust changes in tissue patterning and architecture.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

Recommended Citation

Palmquist, Karl H., "Investigating the Supracellular Processes Underlying Emergent Material Phase Properties During Embryonic Skin Morphogenesis" (2024). Student Theses and Dissertations. 771.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/771