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Biomedical subjects

U Lendahl

Publications and source records attributed to U Lendahl.

94 records · Page 6Linked to original sources

The use of cell lines in neurobiology.

The mature nervous system is made up of a large number of terminally differentiated neuronal and glial cell types, which develop from precursor cells in the embryonic nervous system. Many aspects of the differentiation pathways leading to the formation of neurons and glia remain elusive because of the cellular and molecular complexity of the brain, with cells of different types intermingled and differentiating at different times. One way to reduce the complexity is to study particular developmental stages and steps in neuronal differentiation in cell lines, i.e. clonal, homogeneous populations of cells that can be grown indefinitely in vitro. Urban Lendahl and Ronald McKay discuss how cell lines are used to dissect the cellular differentiation of the nervous system. Recent technical progress may allow the construction of 'custom-made' cell lines from different regions and developmental stages in the nervous system. Such cell lines retain features of the cells from which they originated and make possible detailed molecular studies of features only transiently present in the developing brain. New strategies are being developed which can be used to assess the effect of genetic changes in cell lines both in tissue culture and in the whole animal. This review attempts to show that cell lines are not a 'reductio ad absurdum' but an additional and critical tool in understanding the genetic contribution to the organization and function of the brain.

Animals↗

Conserved and nonconserved structures in the secretory proteins encoded in the Balbiani ring genes of Chironomus tentans.

The large, repetitive Balbiani ring (BR) genes, BR 1, 2, and 6, in Chironomus tentans originated from a short ancestral sequence and have all evolved according to analogous amplification schemes. We analyzed the structures of the BR-encoded secretory proteins and defined the parts that have been conserved during the evolutionary process. The BR products show striking similarities, with the BR 1 and BR 2 products being more similar to each other than to the BR 6 product. In the constant (C) region of the repeat units, 7 of the 30 amino acid residues are strictly conserved; 4 of these are the cysteine residues. The subrepeat (SR) regions of all the BR products are dominated by repeated tripeptide elements rich in proline and charged amino acid residues. Most of the amino acid replacements in both regions are conservative. Secondary structure predictions suggested that the C regions of the BR 1 and BR 2 products have several elements of secondary structure: an alpha-helix, a beta-strand, and one or two reverse turns, as in "globular structures." The prediction for the C region of the BR 6 product is similar but lacks a beta-strand. The predictions for the intervening SR regions appear less conclusive, but are clearly different from those for the C regions, and suggest regular structures not differing in their conformational elements. The SR regions evolved from an ancestor sequence similar to the C region; thus, the BR products seem to represent an example of evolution from one structure to two differently folded products.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Balbiani ring 6 gene in Chironomus tentans: a diverged member of the Balbiani ring gene family.

We describe the internal organization of a large part of the Balbiani ring (BR) 6 gene in Chironomus tentans. The BR6 gene is a diverged member of the BR gene family. It displays the characteristic hierarchic organization of repetitive sequences, but in the constant region of the repeat units the overall sequence homology is only 49% when compared to other BR genes. All four cysteines are among the few amino acids conserved in the constant region. In the subrepeat region the central part is built from a repeated tripeptide, Pro-Glu--Arg+. A similar charge distribution adjacent to prolines is found in other BR gene subrepeat regions, most pronouncedly in the BR2-encoded protein. These conserved properties of the BR gene products are relevant to the issue how the various BR gene products interact to form a supramolecular structure, the larval tube, and how functional demands influence the evolution of a eucaryotic gene family.

Animals↗

The Balbiani ring 2 gene in Chironomus tentans is built from two types of tandemly arranged major repeat units with a common evolutionary origin.

The internal structure of the 37 kb long Balbiani ring 2 (BR 2) gene in Chironomus tentans has been studied by analysis of a collection of cloned cDNA sequences and in genomic Southern blot analysis with the cDNA sequences used as probes. The BR 2 gene contains two types of tandemly arranged major repeat units 200 bp long, represented in our study by the pCt 7 and the pCt 63 cDNA inserts. The pCt 7 major repeat units are arranged in one or possibly a few blocks and cover 10 kb of the gene; the pCt 63 units form one uninterrupted block, 22 kb in length. Genomic Southern blot hybridizations revealed a number of sequence variants of the pCt 7 major repeat unit. In contrast, the 100 copies of the pCt 63 major repeat unit seem to be almost identical. The pCt 7 major repeat unit, 180 bp in length, is organized in the same way as the previously described 215 bp long pCt 63 major repeat, i.e., it contains a repetitive and a non-repetitive part. Moreover, the two major repeat units show a high degree of sequence homology, indicating that the pCt 7 and pCt 63 sequence blocks within the Br 2 gene have evolved through stepwise amplification from a common ancestral sequence.

Journal Article↗