Rap1 GTPase promotes coordinated collective cell migration in vivo.

During development and in cancer, cells often move together in small to large collectives. To move as a unit, cells within collectives need to stay coupled together and coordinate their motility. How cell collectives remain interconnected and migratory, especially when moving through in vivo environments, is not well understood. The genetically tractable border cell group undergoes a highly polarized and cohesive cluster-type migration in the Drosophila ovary. Here we report that the small GTPase Rap1, through activation by PDZ-GEF, regulates border cell collective migration. We find that Rap1 maintains cell contacts within the cluster, at least in part by promoting the organized distribution of E-cadherin at specific cell-cell junctions. Rap1 also restricts migratory protrusions to the front of the border cell cluster and promotes the extension of protrusions with normal dynamics. Further, Rap1 is required in the outer migratory border cells but not in the central nonmigratory polar cells. Such cell specificity correlates well with the spatial distribution of the inhibitory Rapgap1 protein, which is higher in polar cells than in border cells. We propose that precisely regulated Rap1 activity reinforces connections between cells and polarizes the cluster, thus facilitating the coordinated collective migration of border cells.

Identification of maternally-loaded RNA transcripts in unfertilized eggs of Tribolium castaneum.

BACKGROUND: Maternal RNAs play a critical role in early development. Variation in the diversity and levels of maternally derived gene transcripts may be central to the origin of phenotypic novelty -- a longstanding problem in evolution and development. By studying maternal transcriptomes within and between divergent species, a better understanding of the evolutionary forces acting on maternal RNA allocation is possible. RESULTS: We present the first maternal transcriptome of the red flour beetle, Tribolium castaneum. Using a tiled whole-genome microarray, we found that 58.2% of T. castaneum genes are maternally loaded into eggs. Comparison of known Drosophila melanogaster maternal genes to our results showed widespread conservation of maternal expression with T. castaneum. Additionally, we found that many genes previously reported as having sex or tissue specific expression in T. castaneum were also maternally loaded. Identification of such pleiotropy is vital for proper modeling and testing of evolutionary theory using empirical data. The microarray design also allowed the detection of 2315 and 4060 novel transcriptionally active regions greater in length than 100 bp in unfertilized and fertilized T. castaneum eggs, respectively. These transcriptionally active regions represent novel exons of potentially unknown genes for future study. CONCLUSIONS: Our results lay a foundation for utilizing T. castaneum as a model for understanding the role of maternal genes in evolution.

Evidence of a paucity of genes that interact with the mitochondrion on the X in mammals.

Mitochondria are essential organelles whose replication, development, and physiology are dependent upon coordinated gene interactions with both the mitochondrial and the nuclear genomes. The evolution of coadapted (CA) nuclear-mitochondrial gene combinations would be facilitated if such nuclear genes were located on the X-chromosome instead of on the autosomes because of the increased probability of cotransmission. Here, we test the prediction of the CA hypothesis by investigating the chromosomal distribution of nuclear genes that interact with mitochondria. Using the online genome database BIOMART, we compared the density of genes that have a mitochondrion cellular component annotation across chromosomes in 16 vertebrates. We find a strong and highly significant genomic pattern against the CA hypothesis: nuclear genes interacting with the mitochondrion are significantly underrepresented on the X-chromosome in mammals but not in birds. We interpret our findings in terms of sexual conflict as a mechanism that may generate the observed pattern. Our finding extends single-gene theory for the evolution of sexually antagonistic genes to nuclear-mitochondrial gene combinations.