Technology

RNomics: an experimental approach that identifies 201 candidates for novel, small, non-messenger RNAs in mouse. Huttenhofer, A. et al. EMBO J. 20, 2943–2953 (2001) [PubMed]

Small non-messenger (snm) RNAs have a role in cellular physiology, translation and splicing. Because they are difficult to find by the computational analysis of genomic sequences, Huttenhoffer et al. took an EST-like approach to isolate 50–500-nucleotide-long expressed RNA sequences from mouse cells. Among the 201 novel candidates found were small nucleolar RNAs that guide RNA ribose methylation and pseudouridylation and those that modify spliceosomal small nuclear RNA. Some snmRNAs were tissue specific, indicating a new role for snmRNAs in gene expression.

Developmental biology

A crucial component of the endoderm formation pathway, CASANOVA is encoded by a sox -related gene. Dickmeis, T. et al. Genes Dev. 15, 1487–1492 (2001)

casanova encodes a novel Sox-related protein necessary and sufficient for early endoderm formation in zebrafish. Kikuchi, Y. et al. Genes Dev. 15, 1493–1505 (2001)

Several zebrafish mutations disrupt endoderm formation, many of which are in the Nodal signalling pathway. Of these endoderm mutants, casanova (cas) has the most severe endoderm phenotype — it fails to express markers of endoderm differentiation or formation and does not form gut tissue. These studies identify cas as a novel sox-related gene — Kikuchi et al. found it by a positional-cloning and candidate-gene approach, and Dickmeis et al. in a subtractive screen for Nodal-responsive genes — and show that it is the principal effector of Nodal signalling in zebrafish endoderm formation. For example, Kikuchi et al. report that cas can induce sox17 expression, an early endoderm marker, in mutants that cannot respond to Nodal signalling, and that its ectopic expression causes mesodermal cells to switch fate to endoderm.

Technology

Microarrays of cells expressing defined cDNAs. Ziauddin, J. & Sabatini, D. M. Nature 411, 107–110 (2001) [PubMed]

Rapid analysis of gene function is a priority in the post-genomic era. This paper reports the development of a new microarray technique that involves culturing mammalian cells on glass slides that have been printed with arrays of cDNAs in expression vectors. These 'living arrays' can be screened for cellular phenotypes because the cells become transfected with the expression constructs. In a test experiment, the authors identified proteins involved in tyrosine kinase signalling, apoptosis and cell signalling. This approach could be used to identify drug targets and new proteins that alter cell physiology.