Early B-cell factors 2 and 3 (EBF2/3) regulate early migration of Cajal–Retzius cells from the cortical hem

Francesca Chiara,Aurora Badaloni,Laura Croci,Mason L Yeh,Anna Cariboni,Anna Hoerder-Suabedissen,G Giacomo Consalez,Britta Eickholt,Tomomi Shimogori,John G Parnavelas,Sonja Rakić

doi:10.1016/j.ydbio.2012.02.034

Abstract

Cajal–Retzius (CR) cells play a crucial role in the formation of the cerebral cortex, yet the molecules that control their development are largely unknown. Here, we show that Ebf transcription factors are expressed in forebrain signalling centres—the septum, cortical hem and the pallial–subpallial boundary—known to generate CR cells. We identified Ebf2, through fate mapping studies, as a novel marker for cortical hem- and septum-derived CR cells. Loss of Ebf2 in vivo causes a transient decrease in CR cell numbers on the cortical surface due to a migratory defect in the cortical hem, and is accompanied by upregulation of Ebf3 in this and other forebrain territories that produce CR cells, without affecting proper cortical lamination. Accordingly, using in vitro preparations, we demonstrated that both Ebf2 and Ebf3, singly or together, control the migration of CR cells arising in the cortical hem. These findings provide evidence that Ebfs directly regulate CR cell development.

Highlights

The cerebral cortex is a highly organized structure, subdivided in radial and tangential domains, and involved in complex functions such as cognition, sensory processing and motor control
Ebf2 expression did not coincide with Reelin expression in the piriform cortex (PCx) (Fig. 1I); we hypothesised that Ebf2+ signal in this area does not represent CR cells, but rather fibers of the lateral olfactory tract (Corradi et al, 2003)
According to Imayoshi et al (2008), the choroid plexus (ChP) gives rise to a subpopulation of Lhx5+ and Reelin+ CR cells that eventually migrate into the PCx

Summary

Introduction

The cerebral cortex is a highly organized structure, subdivided in radial (layers) and tangential (areas) domains, and involved in complex functions such as cognition, sensory processing and motor control. There is emerging evidence that Cajal–Retzius (CR) cells, the earliest neurons generated in the developing cortex, play a crucial role in both its laminar (Cooper, 2008; Rice and Curran, 2001; Soriano and Del Rio, 2005; Tissir and Goffinet, 2003) and areal (Bielle et al, 2005; Griveau et al, 2010; Meyer et al, 2004) specification. Cajal–Retzius cells arise in a number of forebrain signalling centres, such as the cortical hem (CH) (Garcia-Moreno et al, 2007; TakiguchiHayashi et al, 2004), septum/retrobulbar area and pallial–subpallial boundary (PSPB; known as the anti-hem) (Bielle et al, 2005) and, following tangential migration, populate the entire cortical surface (Bielle et al, 2005; Yoshida et al, 2006).

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Conclusion