Cajal-retzius cells: Recent advances in identity and function.

Cajal-Retzius cells (CRs) are a transient neuronal type of the developing cerebral cortex. Over the years, they have been shown or proposed to play important functions in neocortical and hippocampal morphogenesis, circuit formation, brain evolution and human pathology. Because of their short lifespan, CRs have been pictured as a purely developmental cell type, whose production and active elimination are both required for correct brain development. In this review, we present some of the findings that allow us to better appreciate the identity and diversity of this very special cell type, and propose a unified definition of what should be considered a Cajal-Retzius cell, especially when working with non-mammalian species or organoids. In addition, we highlight a flurry of recent studies pointing to the importance of CRs in the assembly of functional and dysfunctional cortical networks.

Repurposing of the multiciliation gene regulatory network in fate specification of Cajal-Retzius neurons.

Cajal-Retzius cells (CRs) are key players in cerebral cortex development, and they display a unique transcriptomic identity. Here, we use scRNA-seq to reconstruct the differentiation trajectory of mouse hem-derived CRs, and we unravel the transient expression of a complete gene module previously known to control multiciliogenesis. However, CRs do not undergo centriole amplification or multiciliation. Upon deletion of Gmnc, the master regulator of multiciliogenesis, CRs are initially produced but fail to reach their normal identity resulting in their massive apoptosis. We further dissect the contribution of multiciliation effector genes and identify Trp73 as a key determinant. Finally, we use in utero electroporation to demonstrate that the intrinsic competence of hem progenitors as well as the heterochronic expression of Gmnc prevent centriole amplification in the CR lineage. Our work exemplifies how the co-option of a complete gene module, repurposed to control a distinct process, may contribute to the emergence of novel cell identities.