Abstract
The brain is organized morphologically and functionally into a columnar structure. According to the radial unit hypothesis, neurons from the same lineage form a radial unit that contributes to column formation. However, the molecular mechanisms that link neuronal lineage and column formation remain elusive. Here, we show that neurons from the same lineage project to different columns under control of Down syndrome cell adhesion molecule (Dscam) in the fly brain. Dscam1 is temporally expressed in newly born neuroblasts and is inherited by their daughter neurons. The transient transcription of Dscam1 in neuroblasts enables the expression of the same Dscam1 splice isoform within cells of the same lineage, causing lineage-dependent repulsion. In the absence of Dscam1 function, neurons from the same lineage project to the same column. When the splice diversity of Dscam1 is reduced, column formation is significantly compromised. Thus, Dscam1 controls column formation through lineage-dependent repulsion.
Highlights
The brain is organized morphologically and functionally into a columnar structure
As a potential candidate molecule that could regulate this process, we focus on Down syndrome cell adhesion molecule (Dscam), a gene significantly contributing to the phenotypes observed in Down syndrome[20,21]
Our findings suggest a function of Dscam[1] in lineage-dependent repulsion, which provides a link between temporal patterning, neuronal lineage and column formation
Summary
The brain is organized morphologically and functionally into a columnar structure. According to the radial unit hypothesis, neurons from the same lineage form a radial unit that contributes to column formation. We show that neurons from the same lineage project to different columns under control of Down syndrome cell adhesion molecule (Dscam) in the fly brain. The radial unit hypothesis was proposed to explain the mechanism of column formation in the mammalian cerebral cortex. According to this hypothesis, columns are formed by clonally related neurons that are produced from a common progenitor cell[4]. Developmental mechanisms of columnar unit formation and significance of the neuronal lineage remain elusive. The fly visual system shows columnar organizations such as ommatidia in the retina, cartridges in the lamina, and columns in the medulla[7,8,9,10]. The development of ommatidia and lamina cartridges does not accompany NB and lineage-dependent development
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