Abstract
Skeletal condensation occurs when specified mesenchyme cells self-organize over several days to form a distinctive cartilage template. Here, we determine how and when specified mesenchyme cells integrate mechanical and molecular information from their environment, forming cartilage condensations in the pharyngeal arches of chick embryos. By disrupting cytoskeletal reorganization, we demonstrate that dynamic cell shape changes drive condensation and modulate the response of the condensing cells to Fibroblast Growth Factor (FGF), Bone Morphogenetic Protein (BMP) and Transforming Growth Factor beta (TGF-β) signaling pathways. Rho Kinase (ROCK)-driven actomyosin contractions and Myosin II-generated differential cell cortex tension regulate these cell shape changes. Disruption of the condensation process inhibits the differentiation of the mesenchyme cells into chondrocytes, demonstrating that condensation regulates the fate of the mesenchyme cells. We also find that dorsal and ventral condensations undergo distinct cell shape changes. BMP signaling is instructive for dorsal condensation-specific cell shape changes. Moreover, condensations exhibit ventral characteristics in the absence of BMP signaling, suggesting that in the pharyngeal arches ventral morphology is the ground pattern. Overall, this study characterizes the interplay between cytoskeletal dynamics and molecular signaling in a self-organizing system during tissue morphogenesis.
Highlights
A major objective in the skeletogenic field is to understand the sequential mechanisms that direct specification, condensation and overt differentiation during skeletal chondrogenesis
We investigated three questions related to the nature of the condensation process, (1) the timing and nature of dynamic cytoskeletal re-organization in specified prechondrogenic cells; (2) the identity of the principle molecular signaling pathways during cytoskeletal reorganization; and (3) and the effect of cytoskeletal reorganization on downstream gene expression required for chondrocyte differentiation
Our results demonstrate that ROCK and Myosin II driven actomyosin contractions and differential cell cortex tension within the prechondrogenic mesenchyme drives cytoskeletal rearrangements, and the resultant cell shape changes are a prerequisite for mesenchymal condensation
Summary
A major objective in the skeletogenic field is to understand the sequential mechanisms that direct specification, condensation and overt differentiation during skeletal chondrogenesis. Local signaling from adjacent epithelia specify prechondrogenic fate in neural crest-derived mesenchyme, which differentiate into chondrocytes several days later [1]. The critical intermediate step between specification and overt differentiation is condensation, which has two important features: firstly, mechanical forces control cell shape and organization, setting the characteristic size and shape of skeletal elements and concurrently modulate cell fate. Cytoskeletal Reorganization Drives Mesenchymal Condensation design, data collection and analysis, decision to publish, or preparation of the manuscript
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