Speaker
Description
During development, cells migrate throughout the body along morphogenesis, often encountering mechanical stress that deforms their nuclei, potentially influencing gene expression. In zebrafish embryos, trunk neural crest cells (TNCs) are an embryonic cell type that serves as an ideal model for studying in vivo cell squeezing. They originate from a progenitor region with large interstitial spaces (10–12 µm) and migrate into a channel narrower than 3 µm between surrounding tissues. TNCs acquire different fates depending on their position in the migratory chain, with leader cells preferentially becoming neurons and followers acquiring glial or pigment cells.
In this study, using live imaging of transgenic zebrafish and immunostaining, I observed that leader cells deform their nucleus more often and for longer than follower cells. Leaders gradually lower the expression levels of H3K9me3 constitutive heterochromatin as they migrate, possibly in response to confinement, and undergo adaptive softening of the nucleus. Conversely, in zebrafish spadetail mutant embryos, where somite tissue is reduced, the H3K9me3 remains highly expressed. Thus, I hypothesise that mechanical deformation of the nucleus experienced by TNCs might influence cell fate choices by affecting chromatin compaction and, in turn, its accessibility to transcription factors.
Next, I performed single-molecule imaging of neural crest–specific H2B dynamics and live tracking of CBX1 (heterochromatin formation) puncta to compare histone mobility between pre-migratory and migrating TNCs. Furthermore, using neural crest–specific transgenic H2B-Dendra2 zebrafish, I can track the specific photoconverted cells to observe whether nuclear deformation correlates with their neuronal, glial, or pigment cell fates by HCR of fate-specific markers (i.e., Phox2bb for sympathetic neurons, Sox10 for glia, and mitfa for pigment).
Together, this ongoing work integrates nuclear squeezing, chromatin reorganisation, and fate specification, aiming to uncover how mechanical forces regulate gene expression programs during in vivo confined cell migration.
