Molecular mechanisms governing the development of the entorhinal cortex

内嗅皮层包括许多空间调谐细胞，包括网格细胞、头部方向细胞和边缘细胞，其活动支持空间导航和空间记忆。神经元的连接和局部微电路才刚刚开始被研究，内嗅皮层的发育仍然是未知领域。这是令人惊讶的，考虑到有关发育方面的知识可以深入了解不同细胞类型的功能及其参与病理生理过程。内嗅皮层最有趣的解剖学特征之一是其模块化结构，该结构通过几种脊椎动物物种（包括啮齿动物、猴和人类）中的分子标记表达揭示。因此，表达钙结合蛋白的不同兴奋性神经元在浅层中以规则组织的模块（列）排列，并且它们被表达Reelin的另一类兴奋性神经元包围。研究内嗅皮层的发育将揭示内在的组织原则，因为内嗅皮层不接受丘脑的输入，这可能至少部分地解释了皮层结构（如体感或视觉皮层）的柱状/图案化组织。我们将研究控制钙结合蛋白和Reelin阳性神经元迁移及其组织成柱状结构的潜在分子原理。这两个神经元群体的不同之处在于它们的产生高峰、最终目的地和浅层内的局部连接。最有趣的是在胚胎发育过程中，钙结合蛋白和Reelin阳性神经元迁移所需的分子信号的差异。从拟议的发展研究的见解远远超出了更好地了解内嗅皮层功能。因此，我们一方面将确定规范神经元回路生成的基础原则，另一方面也可能更好地理解是什么使这个大脑区域在阿尔茨海默病的早期临床阶段非常敏感。

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.