Specification of Somatosensory Area Identity in Cortical Explants

Abstract

The H-2Z1 transgene is restricted to a subset of layer IV neurons in the postnatal mouse cortex and delineates exactly the somatosensory area. Expression of the H-2Z1 transgene was used as an areal marker to determine when the parietal cortex becomes committed to a somatosensory identity. We have shown previously that grafts dissected from embryonic day 13.5 (E13.5) H-2Z1 cortex and transplanted into the cortex of nontransgenic newborns express H-2Z1 according to their site of origin. Expression was not modified on heterotopic transplantation (). In the present study, whole cortical explants were isolated at E12.5 from noncortical tissues. The explants developed a regionalized expression of H-2Z1, indicating that regionalization takes place and is maintained in vitro. We used this property and confronted embryonic H-2Z1 cortex with presumptive embryonic sources of regionalizing signals in an in vitro grafting procedure. A great majority of E11.5-E13.5 grafts maintained their presumptive expression of H-2Z1 when grafted heterotopically on nontransgenic E13.5-E15.5 explants. However, a significantly lower proportion of E11.5 parietal grafts expressed H-2Z1 in occipital compared with parietal cortex, indicating that somatosensory identity may be partially plastic at E11.5. Earlier stages could not be tested because the E10.5 grafts failed to develop in vitro. The data suggest that commitment to the expression of a somatosensory area-specific marker coincides with the onset of neurogenesis and occurs well before the birth of the non-GABAergic neurons that express H-2Z1 in vivo.

Integration of H-2Z1, a Somatosensory Cortex-Expressed Transgene, Interferes with the Expression of theSatb1andTbc1d5Flanking Genes and Affects the Differentiation of a Subset of Cortical Interneurons

“…However, at the cellular level, coexpression of H-2Z1 transgene with Satb1 was limited. We previously reported that H-2Z1 does not colocalize with Gad-67 transcripts or with the calcium binding proteins parvalbumin and calretinin in the cerebral cortex of P7 C57/CBA transgenics (Gitton et al, 1999a). In contrast, we find here that Satb1 is expressed in a subpopulation of cortical GABAergic interneurons, confirming the limited overlap between Satb1-and H-2Z1-positive cells.…”

“…We observed a progressive extension of Satb1 labeling from the bottom of the barrels to more superficial regions of the barrelfield (Fig. 3B, P3 to P9), a pattern consistent with that of H-2Z1 in C57/CBA mice (Gitton et al, 1999a). Thus, the pattern of expression of H-2Z1 in C57/CBA transgenics consists in a subdomain of that of Satb1.…”

“…In addition, we observed that Plc-l2 ( Fig. 2 A, Plc-l2) was enriched in the barrel walls, a pattern similar to that of H-2Z1 (Gitton et al, 1999a). Expression of Btg3 on flat mounts ( Fig.…”

“…Therefore, the specific somatosensory expression of H-2Z1 C57/ CBA may result from the interplay between H-2K b upstream region and Satb1 regulatory modules. On top of that, modulation of transgene expression by genetic modifiers unraveled by this study and by Gitton et al (1999a) may also participate in the establishment of the unique cortical expression profile of the H-2Z1 transgenic line. Interestingly, two recently published transgenic lines exhibit somatosensory area-specific expression (Lazutkin et al, 2007;Liao and Xu, 2008).…”

“…During development, the parietal cortex becomes competent for H-2Z1 expression at the time when areal identity is set in the developing cerebral cortex (Gitton et al, 1999a). Once turned on, shortly after birth, expression of the transgene is maintained lifelong (Gitton et al, 1999a).…”