Analysis of zebrafish sidetracked mutants reveals a novel role for Plexin A3 in intraspinal motor axon guidance.

One of the earliest guidance decisions for spinal cord motoneurons occurs when pools of motoneurons orient their growth cones towards a common, segmental exit point. In contrast to later events, remarkably little is known about the molecular mechanisms underlying intraspinal motor axon guidance. In zebrafish sidetracked (set) mutants, motor axons exit from the spinal cord at ectopic positions. By single-cell labeling and time-lapse analysis we show that motoneurons with cell bodies adjacent to the segmental exit point properly exit from the spinal cord, whereas those farther away display pathfinding errors. Misguided growth cones either orient away from the endogenous exit point, extend towards the endogenous exit point but bypass it or exit at non-segmental, ectopic locations. Furthermore, we show that sidetracked acts cell autonomously in motoneurons. Positional cloning reveals that sidetracked encodes Plexin A3, a semaphorin guidance receptor for repulsive guidance. Finally, we show that sidetracked (plexin A3) plays an additional role in motor axonal morphogenesis. Together, our data genetically identify the first guidance receptor required for intraspinal migration of pioneering motor axons and implicate the well-described semaphorin/plexin signaling pathway in this poorly understood process. We propose that axonal repulsion via Plexin A3 is a major driving force for intraspinal motor growth cone guidance.

Long-range patterns of diversity and linkage disequilibrium surrounding the maize Y1 gene are indicative of an asymmetric selective sweep.

Both yellow and white corn occurs among ancestral open pollinated varieties. More recently, breeders have selected yellow endosperm variants of maize over ancestral white phenotypes for their increased nutritional value resulting from the up-regulation of the Y1 phytoene synthase gene product in endosperm tissue. As a result, diversity within yellow maize lines at the Y1 gene is dramatically decreased as compared to white corn. We analyzed patterns of sequence diversity and linkage disequilibrium in nine low copy regions located at varying distances from the Y1 gene, including a homolog of the barley Mlo gene. Patterns consistent with a selective sweep, such as significant associations of informative single-nucleotide polymorphisms with endosperm color phenotype, linkage disequilibrium, and significantly reduced diversity within the yellow endosperm haplotypes, were observed up to 600 kb downstream of Y1, whereas the upstream region showed a more rapid recovery. The starch branching enzyme 1 (sbe1) gene is the first region downstream of Y1 that does not have a highly conserved haplotype in the yellow endosperm germplasm.

Contrasting effects of selection on sequence diversity and linkage disequilibrium at two phytoene synthase loci.

We investigated the effects of human selection for yellow endosperm color, representing increased carotenoid content, on two maize genes, the Y1 phytoene synthase and PSY2, a putative second phytoene synthase. Multiple polymorphic sites were identified at Y1 and PSY2 in 75 white and yellow maize inbred lines. Many polymorphic sites showed strong association with the endosperm color phenotype at Y1, but no detectable association was found at PSY2. Nucleotide diversity was equivalent for whites and yellows at PSY2 but was 19-fold less in yellows than in whites at Y1, consistent with the white ancestral state of the gene. The strong sequence haplotype conservation within yellows at Y1 and a significant, negative Tajima's D both verified positive selection for yellow endosperm. We propose that two independent gain-of-function events associated with insertions into the promoter of the Y1 gene and upregulation of expression in endosperm have been incorporated into yellow maize.