New model of cerebral cortex development identified

Researchers provide new data on the role of the protein reelin in the formation of the cortex, the most evolved part of the brain

07-Oct-2022 - Spain

Reelin is a crucial protein in the regulation of neuronal migration and neuronal positioning during brain development. This protein is produced by two types of neurons: Cajal-Retzius neurons during prenatal development and later-emerging GABAergic neurons. Contrary to what was thought until now, where the role of the Cajal-Retzius neurons predominated, this study by the Consejo Superior de Investigaciones Científicas (CSIC) determines that both sources of reelin are essential in corticogenesis, that is, in the formation of the layers of the cerebral cortex.

This work has been possible thanks to the work of the Neurogenesis and cortical expansion group of the Instituto de Neurociencias de Alicante (IN, CSIC-UHM). Contributing to the work of Professor Eduardo Soriano, from the University of Barcelona, researchers at the IN have used two types of mice genetically modified to selectively inactivate the reelin gene in the later-emerging Cajal-Retzius or GABAergic neurons to demonstrate the cooperation of both in the organization of the cerebral cortex.

"Reelin is a protein found mainly in the brain and spinal cord. It is crucial for the regulation of neuronal migration processes and the positioning of neurons in their corresponding layer during embryonic development of the brain and, in particular, of the cerebral cortex," explains Victor Borrell, head of the Neurogenesis and Cortical Expansion group at the IN.

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Reelin is produced by two populations of neurons: on the one hand, Cajal-Retzius neurons, transient cells present exclusively during brain development and which constitute the main source of reelin in the neocortex and hippocampus during prenatal development. And, on the other hand, the GABAergic interneurons, which complement the Cajal-Retzius cells in the production of reelin.

Most neurons are born far from their final destination and must therefore travel long distances, in a process called migration, to reach their final destination. "Reelin has an indispensable role in regulating these processes of migration and positioning of neurons. In addition to this important role in early development, in the adult brain reelin modulates synaptic plasticity and enhances the induction and maintenance of long-term potentiation, an essential process in memory formation," highlights IN researcher and co-author of the discovery Adrian Cardenas.

This new study highlights the important role of gabaergic interneuron-derived reelin in early brain development, particularly in late neuronal migration. The authors observed transient migratory defects, indicating that reelin expressed by either of these two neuronal populations, both Cajal-Retzius cells and GABAergic interneurons, is sufficient to reverse and compensate for some defects in lamination, i.e., in the organization essential for the correct functioning of the cerebral cortex.

Neuronal migration in cognitive disorders

Abnormal neuronal migration is common in many disorders related to cognitive impairment. Recent studies have implicated reelin in the origin and evolution of neurodevelopmental diseases, especially Alzheimer's disease, schizophrenia, bipolar disorder, autism spectrum disorder and epilepsy; at stages where reelin is mainly expressed in GABAergic neurons.

Despite this, the contribution of Reelin expressed by GABAergic interneurons in cortical development is still largely unknown and, consequently, the role of Cajal-Retzius cell-derived reelin might be overemphasized. Therefore, this study was born with the aim of identifying the specific contribution of reelin expressed by each of these two cell populations (Cajal-Retzius and GABAergic) in neuronal migration and cerebral cortex formation.

Traditionally, it has been assumed that while reelin derived from Cajal-Retzius cells is essential for neuronal migration, that produced by interneurons is important for adult neuronal plasticity, as well as being involved in the pathological mechanisms of brain diseases. However, this study concludes that both reelin expressed by Cajal-Retzius cells and that of GABAergic neurons cooperate to orchestrate neuronal migration and corticogenesis.

Note: This article has been translated using a computer system without human intervention. LUMITOS offers these automatic translations to present a wider range of current news. Since this article has been translated with automatic translation, it is possible that it contains errors in vocabulary, syntax or grammar. The original article in Spanish can be found here.

Original publication

Alba Vílchez-Acosta, Yasmina Manso, Adrián Cárdenas, Alba Elías Tersa, Margdalena Martínez-Losa, Marta Pascual, Manuel Álvarez-Dolado, Angus C. Nairn, Víctor Borrell y Eduardo Soriano; "Specific contribution of Reelin expressed by Cajal–Retzius cells or GABAergic interneurons to cortical lamination."; PNAS.

https://www.bionity.com/en/news/1178003/new-model-of-cerebral-cortex-development-identified.html