Integration of temporal and spatial patterning generates neural diversity

Abstract

Summary In the Drosophila optic lobes, 800 retinotopically organized columns in the medulla act as functional units for processing visual information. The medulla contains over 80 types of neurons, which belong to two classes: uni-columnar neurons have a stoichiometry of one per column, while multi-columnar neurons contact multiple columns. We show that combinatorial inputs from temporal and spatial axes generate this neuronal diversity: All neuroblasts switch fates over time to produce different neurons. The neuroepithelium that generates neuroblasts is also sub-divided into six compartments by the expression of specific factors. Uni-columnar neurons are produced in all spatial compartments independently of spatial input; they innervate the neuropil where they are generated. Multi-columnar neurons are generated in smaller numbers in restricted compartments and later move to their final position. The integration of spatial inputs by a fixed temporal neuroblast cascade thus acts as a powerful mechanism for generating neural diversity, regulating stoichiometry and the formation of retinotopy.

Generation and Evolution of Neural Cell Types and Circuits: Insights from the Drosophila Visual System

“…In theory, these mechanisms could explain how at least 20 neuronal types are produced by each neuroblast (Figure 1 d ). Additional mechanisms were required to explain the full diversity of medulla cell types observed (approximately 80), and another recent study (31) has found that some of this additional diversity stems from reginal identity.…”

“…The production of additional cell-type diversity in the medulla takes advantage of regionalized positional information (31). Although all neuroblasts in the OPC progress through the same temporal series, spatially distributed factors modify the types of neurons that are produced in each of at least eight distinct regions along the crescent (Figure 1 e ).…”

“…The two sides (dorsal and ventral) of the crescent express Vsx1, Optix, Dpp, and Wg in mirror symmetry (from the center to the tips), whereas Hh is expressed only in the ventral half. It appears that neural types that are present at a 1:1 ratio with the number of columns in the medulla (unicolumnar neurons) are produced in all compartments independently of spatial input (31). Multicolumnar neurons that span multiple columns and that are fewer in number are produced in spatially restricted domains along the crescent of the OPC, i.e., from fewer neuroblasts.…”

“…Multicolumnar neurons that span multiple columns and that are fewer in number are produced in spatially restricted domains along the crescent of the OPC, i.e., from fewer neuroblasts. These neurons innervate the entire retinotopic map and later move to become distributed across the medulla (31). The combination of temporal and spatial cues thus explains much of the diversity of cell types observed in the medulla.…”

“…These temporal transitions help to generate much of the neural diversity of the medulla. ( e ) Input from regional factors across the OPC produces additional diversity (31). Together, the temporal series plus regionalization produce the highly diverse types of neurons that make up the adult medulla.…”