Molecular mechanisms governing the development of the entorhinal cortex

• Applicant: Professorin Dr. Hannah Monyer
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Developmental Neurobiology
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 381261457

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.

• DFG Programme: Research Grants