Early B-cell factors 2 and 3 (EBF2/3) regulate early migration of Cajal-Retzius cells from the cortical hem.
Bottom Line: 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.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.
Affiliation: Department of Cell and Developmental Biology, University College London, UK.Show MeSH
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Mentions: We next looked for cell-specific expression of YFPEbf2 in the cortex. At E11.5, the PPL is almost entirely populated by migrating CR cells, and YFPEbf2 expression coincided with that of Reelin (Figs. 3A–D′; 30% of YFPEbf2 cells were Reelin+, data not shown) and Calretinin (Calr; Figs. 3E–H′, 39.8% of YFPEbf2 cells were Calr+, data not shown), another marker of CR cells. Earlier studies have shown that Reelin expression in the CH appears after E11.5 (Hanashima et al., 2007; Meyer et al., 2002). Also, it has been shown that the polyclonal anti-Calr antibody, produced by Swant and used in the present experiments, does not recognise a subpopulation of Calr+ CR cells deriving from the septum (Bielle et al., 2005). Thus, it is likely that YFPEbf2+/Reelin+ cells were septum- (Griveau et al., 2010), while YFPEbf2 +/Calr+ were CH-derived CR cells. On the other hand, YFPEbf2+/Reelin− (Fig. 3D′) and YFPEbf2+/Calr− (Fig. 3H′) cells were probably CR cells that originated from the CH and septum, respectively. Finally, YFPEbf2−/Reelin+ (Fig. 3D′) as well as YFPEbf2−/Calr+ (Fig. 3H′) cells could be CR cells that emanated from the PSPB, where Ebf2 was not expressed. A percentage of YFPEbf2+/Calr+ cells detected after E12.5 were SP cells, but these cells were difficult to discriminate from CR cells at early developmental stages; they were found in the SP layer after the splitting of the PPL (Figs. 2G–I). At E13.5, migrating interneurons were also positioned in the MZ (Figs. 3I–L′) and specifically labelled with Calbindin (Calb) antibody. Calbindin immunoreactivity was not detected in YFPEbf2+ cells, suggesting that Ebf2 was not expressed in migrating interneurons (Fig. 3L′). At P7, YFPEbf2 was expressed in CR cells, labelled with Calr antibody in layer I (Figs. 3M,M′). However, a subpopulation of interneurons, expressing Calr postnatally, did not contain YFPEbf2 (Fig. 3M″). YFPEbf2+ cells expressed Nuclear receptor related 1 (Nurr1) (Figs. 3N,N′), a postnatal marker for SP cells, confirming our previous immunohistochemical observations (Figs. 2G–I). Moreover, a small number of YFPEbf2+ cells, seen in the lower parts of developing CP at E13.5 and E16.5 (Figs. 2G,H), were positioned in layers V (Ctip2+; Figs. 3O,O′) and IV (Cux1+; data not shown) postnatally.
Affiliation: Department of Cell and Developmental Biology, University College London, UK.