Telomerase is a multicomponent reverse transcriptase enzyme that adds DNA repeats to the ends of chromosomes using its RNA component as a template for synthesis. Telomerase activity is detected in the germline as well as the majority of tumors and immortal cell lines, and at low levels in several types of normal cells. We have cloned a human gene homologous to a protein from Saccharomyces cerevisiae and Euplotes aediculatus that has reverse transcriptase motifs and is thought to be the catalytic subunit of telomerase in those species. This gene is present in the human genome as a single copy sequence with a dominant transcript of ∼4 kb in a human colon cancer cell line, LIM1215. The cDNA sequence was determined using clones from a LIM1215 cDNA library and by RT-PCR, cRACE and 3′RACE on mRNA from the same source. We show that the gene is expressed in several normal tissues, telomerase-positive post-crisis (immortal) cell lines and various tumors but is not expressed in the majority of normal tissues analyzed, pre-crisis (non-immortal) cells and telomerase-negative immortal (ALT) cell lines. Multiple products were identified by RT-PCR using primers within the reverse transcriptase domain. Sequencing of these products suggests that they arise by alternative splicing. Strikingly, various tumors, cell lines and even normal tissues (colonic crypt and testis) showed considerable differences in the splicing patterns. Alternative splicing of the telomerase catalytic subunit transcript may be important for the regulation of telomerase activity and may give rise to proteins with different biochemical functions.

SUMMARY: 1. It is now clear that members of the fibroblast growth factor (FGF) family have multiple roles during the formation of the central nervous system (CNS).2. There are at least 23 members of the FGF family and, of these, 10 are expressed in the developing CNS, along with four FGF receptors (FGFR‐1–4).3. The present review discusses the roles of these FGFs, with emphasis on FGF‐2, FGF‐8, FGF‐15 and FGF‐17. Fibroblast growth factors‐2 and ‐15 are generally expressed throughout the developing CNS, whereas FGF‐8 and FGF‐17 are tightly localized to specific regions of the developing brain and are only expressed in the embryo during the early phases of proliferation and neurogenesis.4. Expression studies on FGFRs in the chick and mouse indicate that FGFR‐1 is most generally expressed, whereas FGFR‐2 and FGFR‐3 show highly localized but changing patterns of expression throughout CNS development. The FGFR‐4 has been localized to the developing CNS in fish but not at a detailed level, as yet, in chick or mouse.5. A picture is emerging from these studies that particular FGFs signal through specific receptors in a highly localized manner to regulate the development of different regions of the brain.6. This picture has been demonstrated so far for the developing cortex (FGF‐2^–/– mice), the forebrain and midbrain (FGF‐8 hypomorphs) and the cerebellum (FGF‐17/FGF‐8 mutant mice). In addition, generation of mutant animals deleted for FGFR‐1 and FGFR‐2b IIIb demonstrate their importance in FGF signalling.7. However, there are significant gaps in our knowledge of the localization of members of the FGF family and their receptors. More detailed information on the spatio‐temporal mapping of FGFs and FGFR isoforms is required in order to understand the molecular mechanisms through which FGFs signal.

Signals that induce neural cell fate in amniote embryos emanate from a unique cell population found at the anterior end of the primitive streak. Cells in this region express a number of fibroblast growth factors (FGFs), a group of secreted proteins implicated in the induction and patterning of neural tissue in the amphibian embryo. Here we exploit the large size and accessibility of the early chick embryo to analyse the function of FGF signalling specifically during neural induction. Our results demonstrate that extraembryonic epiblast cells previously shown to be responsive to endogenous neural-inducing signals express early posterior neural genes in response to local, physiological levels of FGF signal. This neural tissue does not express anterior neural markers or undergo neuronal differentiation and forms in the absence of axial mesoderm. Prospective mesodermal tissue is, however, induced and we present evidence for both the direct and indirect action of FGFs on prospective posterior neural tissue. These findings suggest that FGF signalling underlies a specific aspect of neural induction, the initiation of the programme that leads to the generation of the posterior central nervous system.