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The transcription factor neurogenin 2 restricts cell migration from the cortex to the striatum

¹ Max-Planck Institute for Neurobiology, Am Klopferspitz 18A, D-82152 Planegg-Martinsried, Germany
² IGBMC, Strasbourg, France

View larger version (82K): [in a new window]   Fig. 1. Ectopic ß-galactosidase-containing cells in the ganglionic eminence of ngn2lacZ/ngn2lacZ mice. Sections of the telencephalon from ngn2lacZKI mice at E14 (A-D,G) and E17 (E,F) showing the expression pattern of ß-galactosidase in blue. (A) ngn2WT/ngn2lacZ heterozygous, and (B) ngn2lacZKI/ngn2lacZKI homozygous littermates. The heterozygous mutant reveals a sharp boundary of X-gal staining between the positive cortex (CTX) and the negative ganglionic eminence (GE), whereas the homozygous mutant contains many ß-galactosidase-positive cells scattered in the GE. The arrow in B indicates the absence of ectopic cells in the ventricular zone (VZ) of the GE, in contrast to later stages (E17; F). CP indicates the cortical plate containing postmitotic neurons. (C) ngn2WT/ngn2lacZ heterozygous, and (D) ngn2GFP/ngn2lacZ homozygous mutant littermates. In the homozygous mutant carrying only one lacZ allele (D), a similar number of ectopic cells are present in the GE, as in the homozygote (B). (E) ngn2WT/ngn2lacZ heterozygous, and (F) ngn2lacZ/ngn2lacZ homozygous littermates at E17. The number of ectopic cells in the GE has increased compared to E14. The arrow in F indicates ectopic cells in the ventricular zone of the GE. (G) Higher magnification of the ectopic cells in the GE of ngn2lacZ/ngn2lacZ homozygous mutants at E14. The arrows indicate cells with morphologies characteristic of migratory neurons. Scale bar in A-F, 100 µm; in G, 25 µm.

View larger version (60K): [in a new window]   Fig. 2. Cortico-striatal cell migration is increased in ngn2lacZ/ngn2lacZ mice. EGFP adenovirus was injected focally in the cortex of a telencephalic slice from wild-type (A) and a homozygous ngn2 mutant littermate (B) at E14. Micrographs were taken 18 hours and 45 hours after the virus injection as indicated in the figure. The phase contrast micrograph and fluorescence micrograph after 18 hours depict the position of the injection site in the cortex and the dashed line indicates the cortico-striatal boundary. Note that cells spread further away from the injection site after 45 hours. No cortical cells have migrated into the GE in the wild-type telencephalic slice, while 4 cortical cells have entered the GE of a ngn2–/– mouse. Scale bars, 200 µm.

View larger version (67K): [in a new window]   Fig. 3. Broadening of the cortico-striatal boundary in ngn2lacZ/ngn2lacZ mice. Cortico-striatal boundary markers as indicated in the panel were detected in sections of telencephali at E16 (A-D) or E14 (E-H) in wild-type (A,C,E,G) and ngn2 homozygous mutant littermates (B,D,F,H). (A-F) Immunostainings for radial glia fibers. Note that the width of the radial glial fascicle (indicated by carets) in A-F and the territory of SFRP2 expression (indicated by arrows) (G,H) are enlarged in the absence of Ngn2. The yellow arrows in E and F indicate the cortico-striatal sulcus.

View larger version (77K): [in a new window]   Fig. 4. Non cell-autonomous effect on cortico-striatal cell migration in ngn2lacZ/ngn2lacZ mice. (A) Example of a homotypic transplantation of a small piece of cortex from a ‘green mouse’ (Okabe et al., 1997) on a ngn2–/– E14 cortex slice fixed after 1 day in vitro. Note that most GFP cells have migrated within the cortex and some of them have crossed the boundary (dashed line) into the GE (arrows). (A’) High power view of part of the explant shown in A (see arrows for reference). (B) Quantification of the cells emigrating from transplants of wild-type cortex on slices from wild-type or ngn2–/– littermates. Note that the overall number of migrating cells, as well as the number of cortical cells entering the GE, is higher on a ngn2–/– substratum compared to wild type. (C) The histogram depicts the proportion of all cells emigrating from the cortex transplants that enter the GE (see B). Note that three times as many migrating cells cross the boundary into the GE on a ngn2–/– substratum than on a wild-type substratum.

View larger version (66K): [in a new window]   Fig. 5. Cortical cells entering the GE in ngn2lacZ/ngn2lacZ mice acquire a ventral identity. (A-D) The cortico-striatal border in sections of the telencephalon from E14 ngn2lacZ/ngn2lacZ mice stained for ß-gal (blue) and hybridized with the probes indicated in the panel (purple ring). Sections are oriented with the cortex to the left and the GE to the right. Double-positive cells are indicated by arrowheads, ß-galactosidase-positive cells negative for the respective transcripts are marked by an arrow. Note that ectopic cells lose expression of cortical genes (lacZ in the ngn2 locus in A and Math2 in B), while they maintain (C) or acquire (D) expression of ventral genes such as Mash1 or Dlx5, respectively.