Reallocation of olfactory Cajal-Retzius cells shapes neocortex architecture

Frutos, Cristina A. de et al.The neocortex undergoes extensive developmental growth, but how its architecture adapts to expansion remains largely unknown. Here, we investigated how early born Cajal-Retzius (CR) neurons, which regulate the assembly of cortical circuits, maintain a dense superficial distribution in the growing neocortex. We found that CR cell density is sustained by an activity-dependent importation of olfactory CR cells, which migrate into the neocortex after they have acted as axonal guidepost cells in the olfactory system. Furthermore, using mouse genetics, we showed that CR cell density severely affects the architecture of layer 1, a key site of input integration for neocortical networks, leading to an excitation/inhibition ratio imbalance. Our study reveals that neurons reenter migration several days after their initial positioning, thereby performing sequential developmental roles in olfactory cortex and neocortex. This atypical process is essential to regulate CR cell density during growth, which in turn ensures the correct wiring of neocortical circuitry. Video AbstractWe are grateful to B. Mathieu and the IBENS Imaging Facility (France BioImaging, supported by ANR-10-INBS-04, ANR-10-LABX-54 MEMO LIFE, and ANR-11-IDEX-0001-02 PSL∗ Research University, “Investments for the future”; NERF N°2011-45; FRM DGE 20111123023; and FRC Rotary International France). We also thank N. Boggetto and the Flow Cytometry platform of the ImagoSeine facility (France BioImaging, supported by ANR-10-INSB-04, “Investments for the future”). C.A.F. was supported by the IEF Marie Curie program and the Labex Memolife, “Investements for the future” (ANR-10-LABX-54 MEMO LIFE and ANR-11-IDEX-0001-02 PSL∗ Research University). G.B. was funded by Labex Memolife, FRM, and Région Ile de France. Y.A. was the recipient of a fellowship from ARC and FRM. The work in P.C. group was supported by FRM (DEQ20121126545) and work in A.P. group by grants from the ANR (ANR-2011-BSV4-023-01) and FRM (DEQ20130326521). This work was supported by grants from MRT, CNRS, INSERM, and the EURYI program to S.G. S.G. is an EMBO YIP awardee and part of the ENP program.Peer Reviewe

Reallocation of Olfactory Cajal-Retzius Cells Shapes Neocortex Architecture.

The neocortex undergoes extensive developmental growth, but how its architecture adapts to expansion remains largely unknown. Here, we investigated how early born Cajal-Retzius (CR) neurons, which regulate the assembly of cortical circuits, maintain a dense superficial distribution in the growing neocortex. We found that CR cell density is sustained by an activity-dependent importation of olfactory CR cells, which migrate into the neocortex after they have acted as axonal guidepost cells in the olfactory system. Furthermore, using mouse genetics, we showed that CR cell density severely affects the architecture of layer 1, a key site of input integration for neocortical networks, leading to an excitation/inhibition ratio imbalance. Our study reveals that neurons reenter migration several days after their initial positioning, thereby performing sequential developmental roles in olfactory cortex and neocortex. This atypical process is essential to regulate CR cell density during growth, which in turn ensures the correct wiring of neocortical circuitry