The Hippo Pathway Regulates Cell Behavior in Capsaspora

Core Concepts

The author argues that the Hippo pathway regulates cell behavior and density in Capsaspora, indicating an ancient mechanism of cell density control preceding animal multicellularity.

Abstract

The study explores the function of the Hippo pathway in Capsaspora, a close unicellular relative of animals. It reveals that upstream Hippo pathway kinases regulate cell behavior and density within multicellular aggregates. The findings suggest an ancestral role of the Hippo pathway in cytoskeletal regulation and cell density control, independent of proliferation.
The research demonstrates that loss of upstream kinases coHpo and coWts leads to increased nuclear localization of coYki, resulting in contractile cell behavior and higher cell packing density within Capsaspora aggregates. This indicates a conserved regulatory mechanism across species for the Hippo pathway.
Furthermore, the study uncovers a novel role for Hippo signaling in regulating cell density through actomyosin-dependent changes in multicellular architecture. These results provide insights into the evolutionary origins and ancestral functions of developmental pathways like the Hippo cascade.
Overall, the research sheds light on how conserved signaling pathways may have operated in unicellular ancestors, offering valuable insights into the regulation of key cellular processes such as cytoskeletal dynamics and cell density control.

Stats

Loss of either kinase results in increased nuclear localization of coYki.
Loss of either kinase causes a contractile cell behavior and increased density of cell packing within Capsaspora aggregates.
Increased density is not due to differences in proliferation but actomyosin-dependent changes.
Transgenic expression of hyperactive coYki mutant results in phenotypes similar to mutants lacking coHpo or coWts.

Quotes

"The Hippo pathway regulates cytoskeletal dynamics but not proliferation in Capsaspora."
"Loss of upstream kinases leads to increased nuclear localization of coYki."
"Hippo signaling may represent an ancient mechanism for controlling cell density."

Key Insights Distilled From

The Hippo kinase cascade regulates a contractile cell behavior and cell density in a close unicellular relative of animals

by Phillips,J. ... at www.biorxiv.org 07-25-2023

https://www.biorxiv.org/content/10.1101/2023.07.25.550562v2

Deeper Inquiries

How does the contractile behavior observed relate to potential environmental influences on Capsaspora cells?

The contractile behavior observed in Capsaspora cells, where they transition from a round morphology to an elongated spindle shape and then contract back to a round form, could be influenced by environmental factors. For instance, the elongated cell morphology was reported to be common after isolation of Capsaspora cells from the B. glabrata snail host. This suggests that environmental cues or signals from the snail host may impact this elongated morphology and potentially affect Hippo pathway signaling in these cells. The dynamic nature of this contractile behavior may serve as an adaptive response to changes in the environment or substrate conditions.

Could variations in filopodial morphology explain differences seen between WT and mutant aggregates?

Variations in filopodial morphology could indeed explain some of the differences observed between WT and mutant aggregates in Capsaspora. Filopodia play a crucial role in mediating adhesion between cells within aggregates, with contacts primarily occurring through interactions between filopodia rather than cell bodies directly contacting each other. In mutant aggregates where there are alterations in filopodial length, density, or structure (such as seen with coWts -/- mutants), it can lead to changes in how cells adhere to each other within the aggregate. These altered interactions at the cellular level can contribute to differences in aggregate shape, size, and packing density compared to WT aggregates.

What implications do these findings have for understanding early mechanisms governing multicellularity?

These findings shed light on early mechanisms governing multicellularity by highlighting conserved pathways involved across different organisms like Capsaspora and animals. The study reveals that Hippo pathway signaling regulates cytoskeletal dynamics but not proliferation control in Capsaspora, indicating an ancestral function related more towards cytoskeletal regulation than proliferation restriction – a key aspect of animal development later on.
Moreover, observations of increased cell packing within mutant aggregates due to actomyosin-mediated contractility suggest shared mechanisms for regulating cell density even before animal multicellularity emerged. This implies that fundamental processes such as contact inhibition might have ancient origins predating complex multicellular life forms like animals.
Understanding these early mechanisms provides insights into how basic cellular behaviors were regulated prior to evolution leading up to modern-day complex organisms with sophisticated developmental processes involving tissue growth control and intercellular communication pathways like those governed by Hippo signaling.