Gregory R. Dressler

OCT-4 - A GERMLINE-SPECIFIC TRANSCRIPTION FACTOR MAPPING TO THE MOUSE T-COMPLEX

Oct‐4 is a maternally expressed octamer‐binding protein encoded by the murine Oct‐4 gene. It is present in unfertilized oocytes, but also in the inner cell mass and in primordial germ cells. Here we show that the ectopic expression of Oct‐4 in HeLa cells is sufficient for transcriptional activation from the octamer motif, indicating that Oct‐4 is a transcription factor. Therefore, Oct‐4 is the first transcription factor described that is specific for the early stages of mouse development. The spatial and temporal expression patterns were further determined using in situ hybridization. With this technique Oct‐4 expression is detected in the oocyte, in the blastocyst and before gastrulation in the embryonic ectoderm. After day 8 Oct‐4 expression decreases and is restricted to primordial germ cells from about day 8.5 onwards. Therefore Oct‐4 is a transcription factor that is specifically expressed in cells participating in the generation of the germline lineage. Linkage analysis using B X D recombinant inbred mouse strains demonstrates that Oct‐4 maps to chromosome 17 in or near the major histocompatibility complex. Several mouse mutants in the distal region of the mouse t‐complex affecting blastocyst and embryonic ectoderm formation also map to this region.

Primary structure and developmental expression pattern of Hox 3.1, a member of the murine Hox 3 homeobox gene cluster.

The murine Hox 3.1 gene maps to a cluster of homeobox‐containing genes on chromosome 15. We report the primary structure of the Hox 3.1 protein, as deduced from cDNA sequences, and the expression of Hox 3.1 mRNA during embryogenesis. In addition, a second member of the gene cluster, Hox 3.2, is characterized. The predicted Hox 3.1 protein consists of 242 amino acid residues and has a calculated mol. wt of 28 kd. Besides the homeodomain, it shares with other murine homeodomain proteins a conserved hexapeptide, a region rich in glutamic acid residues at the carboxy terminus and homology at the amino terminus. During embryogenesis, Hox 3.1 transcripts are detected first in the posterior neural tube of 9.5 days post‐coital embryos. At later developmental stages, a ventral‐dorsal gradient of Hox 3.1 transcript accumulation is established. Hox 3.1 transcripts also are detected in the thoracic sclerotomes from the 6th to the 10th thoracic pre‐vertebrae. The data support the hypothesis that the Hox 3.1 gene specifies positional information during murine embryogenesis.

Do multigene families regulate vertebrate development

The identification of mammalian gene families sharing protein domains with genes that regulate Drosophila embryogenesis could prove to be a major stepping stone towards understanding the genetic basis of mammalian development. Three types of multigene families have already been identified whose expression patterns during embryogenesis are strikingly different from one another. Evidence is accumulating that these multigene families may participate in pattern formation and segmentation of the mammalian embryo.

The regulation of kidney development: new insights from an old model

The embryonic kidney is an excellent model system in which to address many fundamental issues in developmental biology. Inductive interactions are required for proliferation and differentiation of the ureter epithelium and kidney mesenchyme. Recent studies implicate a receptor-type tyrosine kinase as a target of inductive signals in the developing ureter. In the mesenchyme, the early induction response requires at least two transcription factors, WT1 and Pax-2. Through the integrated application of in vitro culture models and gene targeting methods, the molecular mechanisms underlying kidney morphogenesis are becoming clearer.

The primary structure of the murine multifinger gene mKr2 and its specific expression in developing and adult neurons.

The complete amino acid sequence of the murine finger‐containing gene mKr2 was determined. On the basis of sequence similarities in the repeated finger domain, mKr2 belongs to the same class of developmentally expressed genes as Drosophila Krüppel and hunchback. The presence of metal ion and DNA‐binding finger domains similar to those identified in TFIIIA supports the hypothesis that these genes regulate transcription. mKr2 transcripts are restricted to neurons in the central and peripheral nervous system of adult animals. Furthermore, mKr2 transcripts can be detected in all the major structures of the developing nervous system during embryogenesis. The data are consistent with the hypothesis that mKr2 is a regulatory factor required for the differentiation and/or phenotypic maintenance of neurons.

An update on the vertebrate homeobox

Given the complexity of development and the multitude of differentiated cell types in higher eukaryotic organisms, one might expect that a large variety of proteins would be required to regulate specific developmental processes. However, if the differentiated state of a particular cell is specified not by a single protein but by a combination of factors, significantly fewer regulatory proteins are required to constitute a unique genetic program for a single cell type. Furthermore, if the expression level of a single factor, in combination with others, is a determinative event, an even smaller set of governing factors would suffice. Thus considering the finite number of controlling factors, it is remarkable that more and more potential developmental and cellspecific factors contain homeoboxes. While the evidence that vertebrate homeobox genes encode transcription factors active during development is mostly circumstantial, several functionally defined tissue-specific transcription factors have also been found to contain homeobox domains.

Intercellular Signalling: The pros and cons of c-ret

Recent studies of the proto-oncogene c-ret illuminate the basic developmental signalling pathways mediated by receptor tyrosine kinases, as well as the aberrant signalling processes that can lead to cancer.