N-Cadherin Orchestrates Self-Organization of Neurons within a Columnar Unit in the Drosophila Medulla

Abstract

Columnar structure is a basic unit of the brain, but the mechanism underlying its development remains largely unknown. The medulla, the largest ganglion of the Drosophila melanogaster visual center, provides a unique opportunity to reveal the mechanisms of 3D organization of the columns. In this study, using N-cadherin (Ncad) as a marker, we reveal the donut-like columnar structures along the 2D layer in the larval medulla that evolves to form three distinct layers in pupal development. Column formation is initiated by three core neurons, R8, R7, and Mi1, which establish distinct concentric domains within a column. We demonstrate that Ncad-dependent relative adhesiveness of the core columnar neurons regulates their relative location within a column along a 2D layer in the larval medulla according to the differential adhesion hypothesis. We also propose the presence of mutual interactions among the three layers during formation of the 3D structures of the medulla columns.

DWnt4 and DWnt10 Regulate Morphogenesis and Arrangement of Columnar Units via Fz2/PCP Signaling in the Drosophila Brain

“…In our previous study, we showed that R8, R7, and Mi1 are the core columnar neurons that contribute to column formation during the L3 larval stage (Trush et al, 2019). L1-L5 lamina neurons also project to columns at the end of the L3 larval stage.…”

“…In our previous study, we showed that N-cadherin (Ncad) clearly labels medulla columns during development (Liu et al, 2020;Trush et al, 2019). Fmi belongs to the cadherin superfamily and is involved in Wnt/PCP signaling (Usui et al, 1999).…”

“…Celltype-specific overexpression of dsh DN and fz2 DN under the control of R8-Gal4, R7-Gal4, Mi1-Gal4, and L1-5-Gal4 led to irregular columns, as determined by Fmi distribution ( Figures 2J-2N). Expression of these Gal4 drivers begins during L3 larval stage (Trush et al, 2019). Thus, Fz2 and noncanonical Wnt signaling have essential functions in these core columnar neurons.…”

“…Mi1 is one of the earliest neurons that project to the medulla neuropil and is known as an important element of the light edge motion detection pathway (Takemura et al, 2013). We recently demonstrated that Mi1 plays an essential role in medulla column formation (Trush et al, 2019). In addition, the neurites of Mi1 are polarized along with the medulla layers.…”

“…In the following experiments, we labeled the Mi1 neurites using clones expressing bshM-Gal4 UAS-CD8GFP (Trush et al, 2019). Because the donut-like columnar structure is barely detectable in the adult brain, we compared the planar polarity of neurons and column arrangement in pupal brains at 48 h APF.…”