Telencephalic embryonic subtractive sequences: a unique collection of neurodevelopmental genes.

The vertebrate telencephalon is composed of many architectonically and functionally distinct areas and structures, with billions of neurons that are precisely connected. This complexity is fine-tuned during development by numerous genes. To identify genes involved in the regulation of telencephalic development, a specific subset of differentially expressed genes was characterized. Here, we describe a set of cDNAs encoded by genes preferentially expressed during development of the mouse telencephalon that was identified through a functional genomics approach. Of 832 distinct transcripts found, 223 (27%) are known genes. Of the remaining, 228 (27%) correspond to expressed sequence tags of unknown function, 58 (7%) are homologs or orthologs of known genes, and 323 (39%) correspond to novel rare transcripts, including 48 (14%) new putative noncoding RNAs. As an example of this latter group of novel precursor transcripts of micro-RNAs, telencephalic embryonic subtractive sequence (TESS) 24.E3 was functionally characterized, and one of its targets was identified: the zinc finger transcription factor ZFP9. The TESS transcriptome has been annotated, mapped for chromosome loci, and arrayed for its gene expression profiles during neural development and differentiation (in Neuro2a and neural stem cells). Within this collection, 188 genes were also characterized on embryonic and postnatal tissue by in situ hybridization, demonstrating that most are specifically expressed in the embryonic CNS. The full information has been organized into a searchable database linked to other genomic resources, allowing easy access to those who are interested in the dissection of the molecular basis of telencephalic development.

PLAC1, a trophoblast-specific gene, is expressed throughout pregnancy in the human placenta and modulated by keratinocyte growth factor.

Plac1, a placenta-specific gene, is expressed exclusively by cells of trophoblastic lineage in the mouse, and maps to a region of the X chromosome known to be important in placental growth. These studies were undertaken to define the cellular location of the mRNA for the human orthologue, PLAC1, within the human placenta, and to examine its expression throughout gestation. By Northern analysis, PLAC1 mRNA was detected in term human placenta, migrating as a single 1.7 kb transcript, but in no other fetal or adult tissues tested. Expression was observed throughout gestation, whereas mouse Plac1 is significantly reduced after 12.5 dpc. Using an (35)S-labeled riboprobe, PLAC1 expression was trophoblast-specific at all stages of gestation (8-41 weeks); no expression was seen in cells within the stromal compartment or decidua. Using BeWo choriocarcinoma cells as a trophoblast model, keratinocyte growth factor (KGF) stimulated steady-state PLAC1 mRNA expression approximately twofold by Northern analysis and quantitative real-time PCR. Stimulation was observed only after 24 hr of exposure, suggesting that the stimulatory effect of KGF is secondary to the promotion of trophoblast growth or differentiation. No change in mRNA levels resulted from exposure to insulin-like growth factor II (IGF-II). Trophoblast-specific expression throughout gestation and responsiveness to KGF are consistent with a fundamental role for PLAC1 at the maternal-fetal interface.