Biomedical subjects

Ward F Odenwald

Publications and source records attributed to Ward F Odenwald.

7 recordsLinked to original sources

PubMed2005

Regulation of temporal identities during Drosophila neuroblast lineage development.

One of the major goals of neurobiology is to describe, in molecular terms, how a neural progenitor cell can generate an ordered series of uniquely fated neurons and glia. It has become clear that many, or all, neural-subtype identities can be linked to sequentially changing regulatory programs within neural precursors. Recent studies shed light on regulatory inputs and timing mechanisms that generate temporally defined cell identities, and new contributions are beginning to establish a link between the temporal network and cell function.

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PubMed2005

EVOPRINTER, a multigenomic comparative tool for rapid identification of functionally important DNA.

Here, we describe a multigenomic DNA sequence-analysis tool, evoprinter, that facilitates the rapid identification of evolutionary conserved sequences within the context of a single species. The evoprinter output identifies multispecies-conserved DNA sequences as they exist in a reference DNA. This identification is accomplished by superimposing multiple reference DNA vs. test-genome pairwise blat (blast-like alignment tool) readouts of the reference DNA to identify conserved nucleotides that are shared by all orthologous DNAs. evoprinter analysis of well characterized genes reveals that most, if not all, of the conserved sequences are essential for gene function. For example, analysis of orthologous genes that are shared by many vertebrates identifies conserved DNA in both protein-encoding sequences and noncoding cis-regulatory regions, including enhancers and mRNA microRNA binding sites. In Drosophila, the combined mutational histories of five or more species affords near-base pair resolution of conserved transcription factor DNA-binding sites, and essential amino acids are revealed by the nucleotide flexibility of their codon-wobble position(s). Conserved small peptide-encoding genes, which had been undetected by conventional gene-prediction algorithms, are identified by the codon-wobble signatures of invariant amino acids. Also, evoprinter allows one to assess the degree of evolutionary divergence between orthologous DNAs by highlighting differences between a selected species and the other test species.

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PubMed2005

Nerfin-1 is required for early axon guidance decisions in the developing Drosophila CNS.

Many studies have focused on the mechanisms of axon guidance; however, little is known about the transcriptional control of the navigational components that carryout these decisions. This report describes the functional analysis of Nerfin-1, a nuclear regulator of axon guidance required for a subset of early pathfinding events in the developing Drosophila CNS. Nerfin-1 belongs to a highly conserved subfamily of Zn-finger proteins with cognates identified in nematodes and man. We show that the neural precursor gene prospero is essential for nerfin-1 expression. Unlike nerfin-1 mRNA, which is expressed in many neural precursor cells, the encoded Nerfin-1 protein is only detected in the nuclei of neuronal precursors that will divide just once and then transiently in their nascent neurons. Although nerfin-1 null embryos have no discernible alterations in neural lineage development nor in neuronal or glial identities, CNS pioneering neurons require nerfin-1 function for early axon guidance decisions. Furthermore, nerfin-1 is required for the proper development of commissural and connective axon fascicles. Our studies also show that Nerfin-1 is essential for the proper expression of robo2, wnt5, derailed, G-oalpha47A, Lar, and futsch, genes whose encoded proteins participate in these early navigational events.

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PubMed2005

Changing fates on the road to neuronal diversity.

One of the longstanding goals of neurobiologists is to describe, in molecular terms, how a neural progenitor cell (NPC) can generate an ordered series of uniquely fated neurons and glia. Recent studies reveal that many, or all, neural-subtype identities can be linked to sequentially changing regulatory programs within NPCs. Two new studies, in this issue of Developmental Cell, provide novel insights into the molecular details of how Drosophila NPCs transition from one offspring identity program to the next.

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PubMed2003

Mutations that affect the ability of the vnd/NK-2 homeoprotein to regulate gene expression: transgenic alterations and tertiary structure.

The importance in downstream target regulation of tertiary structure and DNA binding specificity of the protein encoded by the vndNK-2 homeobox gene is analyzed. The ectopic expression patterns of WT and four mutant vndNK-2 genes are analyzed together with expression of two downstream target genes, ind and msh, which are down-regulated by vndNK-2. Three mutants are deletions of conserved regions (i.e., tinman motif, acidic motif, and NK-2 box), and the fourth, Y54M vndNK-2, corresponds to a single amino acid residue replacement in the homeodomain. Of the four ectopically expressed mutant genes examined, only the Y54M mutation inactivates the ability of the vndNK-2 homeodomain protein to repress ind and msh. The acidic motif deletion mutant slightly reduced the ability of the protein to repress ind and msh. By contrast, both tinman and NK-2 box deletion mutants behaved as functional vndNK-2 genes in their ability to repress ind and msh. The NMR-determined tertiary structures of the Y54M vndNK-2 homeodomain, both free and bound to DNA, are compared with the WT analog. The only structural difference observed for the mutant homeodomain is in the complex with DNA and involved closer interaction of the methionine-54 with A2, rather than with C3 of the (-) strand of the DNA. This subtle change in the homeodomain-DNA complex resulted in modifications of binding affinities to DNA. These changes resulting from a single amino acid residue replacement constitute the molecular basis for the phenotypic alterations observed on ectopic expression of the Y54M vndNK-2 gene during embryogenesis.

Amino Acid Substitution↗

PubMed2002

Identification of novel Drosophila neural precursor genes using a differential embryonic head cDNA screen.

During Drosophila neuroblast lineage development, temporally ordered transitions in neuroblast gene expression have been shown to accompany the changing repertoire of functionally diverse cells generated by neuroblasts. To broaden our understanding of the biological significance of these ordered transitions in neuroblast gene expression and the events that regulate them, additional genes have been sought that participate in the timing and execution of these temporally controlled events. To identify dynamically expressed neural precursor genes, we have performed a differential cDNA hybridization screen on a stage specific embryonic head cDNA library, followed by whole-mount embryo in situ hybridizations. Described here are the embryonic expression profiles of 57 developmentally regulated neural precursor genes. Information about 2389 additional genes identified in this screen, including 1614 uncharacterized genes, is available on-line at 'BrainGenes: a search for Drosophila neural precursor genes' (http://sdb.bio.purdue.edu/fly/brain/ahome.htm).

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PubMed2002

Cellular diversity in the developing nervous system: a temporal view from Drosophila.

This article considers the evidence for temporal transitions in CNS neural precursor cell gene expression during development. In Drosophila, five prospective competence states have so far been identified, characterized by the successive expression of Hb-->Kr-->Pdm-->Cas-->Gh in many, but not all, neuroblasts. In each temporal window of transcription factor expression, the neuroblast generates sublineages whose temporal identity is determined by the competence state of the neuroblast at the time of birth of the sublineage. Although similar regulatory programs have not yet been identified in mammals, candidate regulatory genes have been identified. Further investigation of the genetic programs that guide both invertebrate and vertebrate neural precursor cell lineage development will ultimately lead to an understanding of the molecular events that control neuronal diversity.

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