In exciting new research just published in Cell Reports, Antonio Jesús Hinojosa, Dr Rubén Deogracias and Professor Beatriz Rico have uncovered a molecular program through which the microtubule-associated kinase, NEK7, commands the shape and wiring of cortical interneurons.
“Interneurons play a key role during the development and function of the cerebral cortex. However, it has been difficult to study them in detail given their sparseness. Gradually, their differential features are starting to be discovered and with this study, we contribute to this knowledge. We identified NEK7 and characterised its role during various steps of PV interneuron development. Nevertheless, NEK7 seems not to act alone but to be part of a wider molecular program that allows for the differential features of these cells. Our work and further research about these mechanisms may help the scientific community understand the uniqueness of interneurons and how their differential development contributes to their final function”
Dr Antonio Hinojosa, first author.
Identifying the mechanisms which dictate precisely how neurons are wired in particular circuits is critical to understand how the extraordinary complexity of brain function emerges. In the mammalian cerebral cortex, the two main classes of neurons, glutamatergic pyramidal cells and GABAergic interneurons, show remarkably different morphology and synaptic targeting which leads to distinct contributions to the cortical network.
The study builds on previous work by Professor Beatriz Rico on how mammalian cortical networks are built and how they function. In the last few years, Beatriz and her lab have shown that cortical GABAergic circuitry is directly involved in cognitive function, and that developmental disruption of the function of cortical interneurons might be linked to the pathophysiology of neurodevelopmental disorders.
“In this new study, we unveil part of the molecular program that command unique behaviors to the PV+ axons allowing them to increase their axonal arbor complexity and possible their efficiency to establish specific connections with the highest possible number of neighbor pyramidal cells. Considering the increasing evidence suggesting that small variations in the development of GABAergic interneurons may lead to neurodevelopmental disorders, the identification of molecules that coordinate the development of these cells not only represents a major scientific advance but also has important biomedical implications”
Professor Beatriz Rico, senior author.