Biomedical subjects

Alexander Kuzin

Publications and source records attributed to Alexander Kuzin.

3 recordsLinked to original sources

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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PubMed2004

Drosophila homeodomain protein Nkx6 coordinates motoneuron subtype identity and axonogenesis.

The regulatory networks acting in individual neurons to control their stereotyped differentiation, connectivity, and function are not well understood. Here, we demonstrate that homeodomain protein Nkx6 is a key member of the genetic network of transcription factors that specifies neuronal fates in Drosophila. Nkx6 collaborates with the homeodomain protein Hb9 to specify ventrally projecting motoneuron fate and to repress dorsally projecting motoneuron fate. While Nkx6 acts in parallel with hb9 to regulate motoneuron fate, we find that Nkx6 plays a distinct role to promote axonogenesis, as axon growth of Nkx6-positive motoneurons is severely compromised in Nkx6 mutant embryos. Furthermore, Nkx6 is necessary for the expression of the neural adhesion molecule Fasciclin III in Nkx6-positive motoneurons. Thus, this work demonstrates that Nkx6 acts in a specific neuronal population to link neuronal subtype identity to neuronal morphology and connectivity.

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