Molecular mechanisms governing the development of the entorhinal cortex

内嗅觉皮质由许多空间调节细胞组成，包括网格细胞、头向细胞和边缘细胞，它们的活动支持空间导航和空间记忆。神经元的连通性和局部微电路才刚刚开始研究，内嗅皮层的发育仍然是未知的。这是令人惊讶的，考虑到关于发育方面的知识既能洞察不同类型细胞的功能，也能洞察它们参与病理生理过程。内嗅觉皮质最耐人寻味的解剖学特征之一是其模块化结构，这是在包括啮齿动物、猴子和人类在内的几种脊椎动物中表达的分子标记所揭示的。因此，表达Calbindin的不同兴奋神经元排列在浅层有规则组织的模块(柱)中，它们被另一类表达Reelin的兴奋神经元包围。研究内嗅觉皮质的发育将揭示内在的组织原理，因为内嗅觉皮质不接受丘脑输入，这可能至少部分解释了柱状/图案化的皮质结构，如躯体感觉或视觉皮质。我们将研究控制Calbindin和Reelin阳性神经元迁移及其组织成柱状结构的潜在分子原理。这两个神经元群体在其产生的峰值、最终目的地和浅层内的局部连接方面有所不同。最耐人寻味的是，在胚胎发育过程中，控制Calbindin和Reelin阳性神经元迁移所需的分子信号有所不同。这项拟议的发育研究的洞察力远远超出了对内嗅觉皮质功能的更好理解。因此，我们一方面将确定规范神经元电路产生的基础原理，另一方面也可能更好地理解是什么使这一大脑区域非常容易受到阿尔茨海默病早期临床阶段的影响。

The entorhinal cortex comprises a number of spatially tuned cells, including grid cells, head direction cells and border cells, whose activity support spatial navigation and spatial memory. Neuronal connectivity and local microcircuits have just begun to be investigated, and the development of the entorhinal cortex has remained terra incognita. This is surprising, considering that knowledge regarding developmental aspects give insight both into function of distinct cell types and their involvement in pathophysiological processes. One of the most intriguing anatomical features of the entorhinal cortex regards its modular structure that is revealed by molecular marker expression in several vertebrate species, including rodents, monkey and human. Thus, distinct excitatory neurons expressing Calbindin are arranged in regularly organized modules (columns) in the superficial layers, and they are surrounded by another class of excitatory neurons that express Reelin. To study the development of entorhinal cortex will reveal intrinsic organizational principles because the entorhinal cortex does not receive thalamic input that may account at least in part for the columnar/patterned organization of cortical structures such as the somatosensory or visual cortex. We will study the underlying molecular principles that govern Calbindin- and Reelin-positive neuron migration and their organization into columnar structures. The two neuronal populations differ with respect to their peak of generation, final destination and local connectivity within the superficial layers. Most intriguing is the difference in the required molecular signaling that governs migration of Calbindin- and Reelin-positive neurons during embryonic development. The insight from the proposed developmental study reaches far beyond a better understanding of entorhinal cortex function. Thus, we will identify principles that underlie the generation of canonical neuronal circuits on one hand and may also gain a better understanding as to what renders this brain area very susceptible already at early clinical stages in Alzheimer disease.