Basement membrane assembly stress initiates Drosophila Central Nervous morphogenesis

• Main Author: Serna Morales, Eduardo
• Format: Dissertation
• Language: English
• Published: King's College London 2022

The basement membrane (BM) is a polymeric network surrounding most tissues. Important for providing physical and biochemical support to the overlying cells, its role in development is assumed to be passive by providing a substrate that allows for the cellular-driven activities that control tissue sculpting. However, all polymer networks can theoretically develop autonomous stresses during assembly, and there is speculation that the BM may play a more active role during tissue morphogenesis that many would assume. Here we exploit Drosophila embryogenesis, which involves a de novo burst of BM polymerization midway through development to examine the role of an out-of-equilibrium BM network during central nervous system morphogenesis. The ventral nerve cord (VNC) of the Drosophila embryo reduces its length in 50% during a period of 12 hours in a process commonly known as VNC condensation. Simultaneously, Drosophila macrophages (hemocytes) migrate along the VNC surface producing and dispersing BM components which are essential for the formation of the nascent layer of BM that wraps the tissue. Asymmetric VNC shortening and a rapid decrease in surface area correlates with exponential assembly of Collagen-IV (Col4). Concomitantly, a transient hemocyte-induced Col4 gradient leads to a coherent long-range BM flow, which equilibrates the Col4 network surrounding the tissue. Finite element analysis and perturbation of the Col4 network through the generation of dominant Col4-truncations that affect assembly, reveal that VNC morphodynamics are driven by a sudden increase in BM-driven surface tension. These data highlight that BM assembly and stress associated network instabilities can directly generate forces that drive tissue morphogenesis.