Molecular anatomy of the entorhinal cortex
- 1Boston University School of Medicine
Abstract
The entorhinal cortex (EC) is critical for episodic memory formation and is the epicenter of neurofibrillary tangle formation in Alzheimer's disease. Its cytoarchitectonic and functional heterogeneity has been recognized for decades, but the molecular underpinnings of this heterogeneity are still relatively uncharted. While many features of the region appear to be conserved between rodents and primates, very little is known about the conservation of the molecular identity of EC neurons. Here we perform single-nucleus RNAseq (snRNAseq) of the mouse EC and use in situ hybridization, as well as publicly available transcriptomics data, to enhance the understanding of the heterogeneity of neuron types present in the area. While the well-known dichotomy between lateral and medial EC is evident in superficial layers of EC, we highlight that the medioventral region of EC forms a different population from the caudomedial section. We identify molecular correlates for the previously described parcellation of lateral EC, and show that, at least in layer IIa, subterritories of EC are not separated by abrupt borders but rather form smooth gradients. Lastly, we show that both lateral vs. medial ECIIa markers, and markers that reveal finer grain heterogeneity within ECIIa have conserved patterns of expression in macaque, highlighting the high degree of homology between the two species. Overall this molecular atlas of the mouse EC with some comparative elements is a resource for anatomically-informed molecular studies of the EC and lays the groundwork for mechanistic studies of selective neuronal vulnerability of the region in the context of AD.
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BibTeX
@misc{morellomegias2026molecular,
title = {{Molecular anatomy of the entorhinal cortex}},
author = {A. Morello-Megias and B. S. Dhulipalla and H. A. Kahvecioglu and J. Shin and S. Joseph and D. Aggarwal and J. I. Luebke and D. L. Rosene and C. Dimovasili and J.-P. Roussarie},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.758661},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.758661v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Molecular anatomy of the entorhinal cortex
AU - A. Morello-Megias
AU - B. S. Dhulipalla
AU - H. A. Kahvecioglu
AU - J. Shin
AU - S. Joseph
AU - D. Aggarwal
AU - J. I. Luebke
AU - D. L. Rosene
AU - C. Dimovasili
AU - J.-P. Roussarie
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.758661
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.758661v1
AB - The entorhinal cortex (EC) is critical for episodic memory formation and is the epicenter of neurofibrillary tangle formation in Alzheimer's disease. Its cytoarchitectonic and functional heterogeneity has been recognized for decades, but the molecular underpinnings of this heterogeneity are still relatively uncharted. While many features of the region appear to be conserved between rodents and primates, very little is known about the conservation of the molecular identity of EC neurons. Here we perform single-nucleus RNAseq (snRNAseq) of the mouse EC and use in situ hybridization, as well as publicly available transcriptomics data, to enhance the understanding of the heterogeneity of neuron types present in the area. While the well-known dichotomy between lateral and medial EC is evident in superficial layers of EC, we highlight that the medioventral region of EC forms a different population from the caudomedial section. We identify molecular correlates for the previously described parcellation of lateral EC, and show that, at least in layer IIa, subterritories of EC are not separated by abrupt borders but rather form smooth gradients. Lastly, we show that both lateral vs. medial ECIIa markers, and markers that reveal finer grain heterogeneity within ECIIa have conserved patterns of expression in macaque, highlighting the high degree of homology between the two species. Overall this molecular atlas of the mouse EC with some comparative elements is a resource for anatomically-informed molecular studies of the EC and lays the groundwork for mechanistic studies of selective neuronal vulnerability of the region in the context of AD.
ER -