Laminin Levels Regulate Tissue Migration and Anterior-Posterior Polarity during Egg Morphogenesis in Drosophila
- Egg development in Drosophila melanogaster provides an excellent model system to study in vivo Basement membranes contribution to organogenesis.
- Integrin-laminin levels fix the timing and speed of egg chamber rotation in vivo.
- Laminin depletion results in anterior-posterior misorientation of developing follicles.
Basement membranes (BMs) are specialized extracellular matrices required for tissue organization and organ formation. We study the role of laminin and its integrin receptor in the regulation of tissue migration during Drosophila oogenesis. Egg production in Drosophila involves the collective migration of follicle cells (FCs) over the BM to shape the mature egg. We show that laminin content in the BM increases with time, whereas integrin amounts in FCs do not vary significantly. Manipulation of integrin and laminin levels reveals that a dynamic balance of integrin-laminin amounts determines the onset and speed of FC migration. Thus, the interplay of ligand-receptor levels regulates tissue migration in vivo. Laminin depletion also affects the ultrastructure and biophysical properties of the BM and results in anterior-posterior misorientation of developing follicles.
When secreted, laminins are proposed to self-assemble through their short arms into networks that recruit the other BM structural components. They remain bonded to the cell surface through the interaction of their long arms with transmembrane receptors, mainly of the integrin family. Interestingly, the finding that mosaic egg chambers containing laminin-mutant FCs generate round eggs at low frequency suggested that laminins could be involved in FC migration and/or egg chamber elongation.
Here we address the role of the balance between integrin and laminin concentrations in epithelial cell migration. By manipulating integrin and laminin levels, we find that the dynamics of laminin-integrin levels regulate the timing and speed of collective migration in vivo. In addition, we unravel a role for BM composition and stiffness in the maintenance of the egg’s AP polarity during oogenesis. Because this is a necessary step required for proper fertilization, our results implicate correct ECM organization in effective fertilization.
Authors: María C. Díaz de la Loza, Alfonsa Díaz-Torres, Federico Zurita, Alicia E. Rosales-Nieves, EmadMoeendarbary, KristianFranze, María D. Martín-Bermudo, Acaimo González-Reyes.
Quantification of Laminin Levels in laminin-Depleted Ovaries
(A) Schematic of an ovariole.
(B and D) Immunodetection of the Laminin β1 subunit in control, laminin hypomorphic, and tj > LanB1 RNA iovarioles. Mutant conditions show significantly lower Laminin β1 levels. Images are maximum Z projections of at least 15 sections.
(C and E) Quantification of the immunofluorescence signal. Mean and SD of at least 14 measurements per genotype and stage are indicated.