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

First Author  Moreau MX Year  2023
Journal  Dev Cell Volume  58
Issue  15 Pages  1365-1382.e6
PubMed ID  37321213 Mgi Jnum  J:338207
Mgi Id  MGI:7510284 Doi  10.1016/j.devcel.2023.05.011
Citation  Moreau MX, et al. (2023) Repurposing of the multiciliation gene regulatory network in fate specification of Cajal-Retzius neurons. Dev Cell
abstractText  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.
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