Molecular mechanisms of columnar unit formation by differential cell adhesion in the brain

柱状结构是大脑的基本单位，但柱状结构的形成机制在很大程度上仍不清楚。在这项研究中，我们根据苍蝇脑中基本柱状神经元之间的不同黏附水平，提出了柱状组织的机制，该黏附分子受细胞黏附分子N-钙粘素(N-cad)和Flamingo(Fmi)的调节。我们揭示了柱的形成是由R8、R7和Mi1三个核心神经元启动的，并根据差异黏附假说(DAH)证明了这些柱状神经元的Ncad依赖的相对黏附调节它们在柱内的相对位置。首先，我们检查了这些神经元中Ncad的水平，发现柱状神经元含有更多的Ncad，顺序为R7&gt；R8&gt；Mi1。然后，我们降低了最粘连的R7神经元中Ncad的水平，发现R7从柱子的中心扩展到柱子的外围区域。当R8神经元的Ncad水平降低时，观察到相似的表型：这些神经元的终末扩张并重定向到柱外的外周区域。相反，在粘附性较弱的Mi1神经元中，Ncad的过度表达导致这些神经元重新定向到柱状中心。Ncad在R8神经元中的过度表达导致R8终末广泛投射到柱中央。此外，我们还建立了一个数学模型，证实了核心柱状神经元的排列完全可以通过这些核心柱状神经元之间的差异性黏附来实现。

Columnar structure is a basic unit of the brain, but the mechanism of column formation remains largely unknown. In this study, we proposed the mechanism of column organization based on the differential level of adhesion between essential columnar neurons in the fly brain, regulated by cell adhesion molecules N-cadherin (N-cad) and Flamingo (Fmi). We revealed that column formation is initiated by three core neurons, R8, R7, and Mi1, and demonstrated that Ncad-dependent relative adhesiveness of these columnar neurons regulates their relative location within a column according to the differential adhesion hypothesis (DAH). First, we examined the level of Ncad in each of these neurons and found that columnar neurons contain more Ncad in the order of R7 > R8 > Mi1. Then, we decreased the level of Ncad in the most adhesive R7 neurons and found that the R7 expands from the center of the column to the peripheral area of the column. When Ncad level was reduced in R8 neurons, similar phenotype was observed: terminals of these neurons expanded and redirected to the peripheral area outside the column. In the contrary, overexpression of Ncad in less adhesive Mi1 neurons induced the redirection of these neurons toward the column center. Ncad overexpression in R8 neurons led to the extensive projection of R8 terminals to the center of the column. In addition, we established a mathematical model that confirms that the arrangement of core columnar neurons can be achieved solely by the differential adhesion between these core columnar neurons.