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ショウジョウバエ原腸胚cephalic furrow形成における空間的パターンと形態形成機構

Eritano, Anthony Stephen 神戸大学

2020.03.05

概要

Background
Establishment of complex biological structures is crucial for embryonic development. These complex structures are form during morphogenesis through dynamic remodeling and folding of epithelial tissues. It is important that these folding and remodeling events can be faithfully reproduced spatially and temporally throughout the population of an organism. While robust morphogenesis is common during embryonic development, the mechanism that underlie this robustness are poorly understood. Robustness of morphogenetic processes relies on the establishment and maintenance of a genetic pattern, which dictates cell behaviors. Next, the cells must interpret the information provided by the genetic pattern. The establishment of the genetic pattern has been shown to be highly refined and spatially precise (Bentovim et al., 2017; Lagha et al., 2012). Additionally, some aspects of embryonic growth and shape changes have been shown to exhibit some level of self-correcting properties (Aliee et al., 2012; Hong et al., 2008; Xiong et al., 2013; Yevick et al., 2019). But it is unclear how morphological precision stems from the apparent spatial information. Specifically, it is unknown if the mechanisms involved in epithelial morphogenesis possess the same kind of self-correcting system that ensures proper morphological events and faithfully interpret the genetic pattern.

Results
In this study, my coauthors and myself conducted a systematic, multiscale characterization of cephalic furrow formation in the Drosophila embryo on a genetic, cell, and tissue scale. By revisiting the known genetic network that regulates cephalic furrow initiation, I have identified additional regulatory elements that further refine the spatial pattern of the cephalic furrow, thus generating highly precise spatial information. Fixed and live imaging analysis on the cellular level shows that cephalic furrow initiation cells display two distinct cell behaviors that are spatially and temporally heterogeneous. However, we found that 80% of these initiating events are specified by the positional information generated by the genetic pattern. The remaining 20% of mis-specified initiation events are attributed to heterogeneous and fluctuating myosin behavior on the cellular scale. Despite this 20% misspecification, a linear cephalic furrow is formed. We also identified a novel myosin behavior in which myosin is localized to the lateral surface of the initiating ells and drives the shrinkage of the lateral membrane. On a tissue scale, the lateral myosin becomes enriched and planar polarized to form supracellular ribbons across the tissue. Using laser ablations and optogenetics, we have shown that the initiating cells are mechanically coupled to each other.

Conclusion and discussion
From this work, I have shown that precise spatial information generated by the genetic patterning of the embryo is vital for ensuring not only the location of cephalic furrow development but also providing necessary cues that lead to specific types of cell behaviors. Despite this precise positional information, heterogeneity in cell behavior still exists in the cells. Removal of this “noise” is accomplished by the mechanical coupling on the initiating cells on the tissue scale. Through this coupling of cells on the tissue scale, the embryo can ensure morphogenetic precision is preserved and consistent despite developmental noise generated during the interpretation of positional information.

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