Nuclear Dynamics During Confined Immune Cell Migration in the Drosophila Pupal Wing

Abstract

During immune surveillance, immune cells regularly encounter confined spaces as they navigate
through complex 3D microenvironments. These environmental constraints pose a physical challenge to migration, as immune cells must travel across basement membranes, squeeze out of
blood vessels and patrol tissues. Efficient migration in these complex and confined environments
thus relies on immune cells dynamically adapting their morphology and migratory style. As the
largest and stiffest organelle, the nucleus represents a key rate-limiting step during migration.
Detailed in vitro studies of nuclear dynamics during confined migration have revealed that some
nuclei are remarkably deformable, even at the detriment of cell health. However, there is a clear
need to study nuclear deformability and its consequences in vivo within physiologically relevant
settings.
Here, I have established the Drosophila melanogaster pupal wing as a novel in vivo model
for detailed mechanistic analysis of nuclear plasticity in Drosophila immune cells (hemocytes) as
they transition from migrating in relatively unrestricted to highly confined environments in vivo.
Integrating live time-lapse imaging and Drosophila’s unrivalled genetic tractability within the
translucent pupal wing, I have shown that pupal wing hemocytes exhibit altered cell morphology
and striking nuclear deformability following pupal wing vein formation. Detailed molecular
analysis of the nuclear lamina composition suggests that hemocytes rely on increased levels of
B-type Lamins to enable these dynamic changes in nuclear shape and to protect the nucleus from
abnormal deformation.
We envision that this novel in vivo model can be harnessed to explore the molecular mechanisms underlying immune cell migration in confinements, and study its long-term consequences
on immune cell health and function. Furthermore, the complex and varied migratory environments within the pupal wing veins offer exciting possibilities to investigate how immune cells
respond to the complex interactions they face during confined migration in vivo.

Date of Award	5 Dec 2023
Original language	English
Awarding Institution	University of Bristol
Supervisor	Helen M A Weavers (Supervisor)