Cilia, ciliopathies and forebrain development

Researchers in the Developmental Biology Unit1 have recently deciphered the role of the cellular primary cilia in the formation of the forebrain2.

Primary cilia are cellular antennas. They receive extracellular signals, transmit them to the cell and modulate different signaling pathways, such as the Hedgehog pathway. Their dysfunctions lead to severe inherited diseases called ciliopathies, which can be characterized by renal and cerebral malformations, obesity, vision and hearing defects, sterility, etc.

The researchers studied a gene known to be associated with human ciliopathies, and looked for its role in the development of the mouse forebrain. They have shown that when this gene is mutated, primary cilia are absent or poorly formed and that this mutation causes serious defects in the development of the fetus, such as a reduction in the ventral forebrain and an absence of the eyes. At the molecular level, the Hedgehog signaling pathway is impacted differently depending on the forebrain region: it can be overactivated or repressed.

This publication provides a better understanding of the role of primary cilia in the development of the forebrain.

In the future it will be interesting to study in greater depth the forebrain defects in human ciliopathies and to look for mutations of ciliopathy genes in other diseases affecting the development of this brain region.

These results were published in The Journal of Neuroscience on January 28, 2019, and were the subject of a CNRS press release.


Team Morphogenesis of the vertebrate brain of the Developmental Biology Laboratory (UMR 7622)

The ciliopathy gene ftm/rpgrip1l controls mouse forebrain patterning via region-specific modulation of hedgehog/gli signaling A. Andreu-Cervera, I. Anselme, A. Karam, C. Laclef, M. Catala, S. Schneider-Maunoury. Journal of Neuroscience, 28 January 2019, 2199-18;