The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells

Observations of rapid shifts in mitochondrial DNA (mtDNA) variants between generations prompted the creation of the bottleneck theory. A prevalent hypothesis is that a massive reduction in mtDNA content during early oogenesis leads to the bottleneck. To test this, we estimated the mtDNA copy number in single germline cells and in single somatic cells of early embryos in mice. Primordial germ cells (PGCs) show consistent, moderate mtDNA copy numbers across developmental stages, whereas primary oocytes demonstrate substantial mtDNA expansion during early oocyte maturation. Some somatic cells possess a very low mtDNA copy number. We also demonstrated that PGCs have more than 100 mitochondria per cell. We conclude that the mitochondrial bottleneck is not due to a drastic decline in mtDNA copy number in early oogenesis but rather to a small effective number of segregation units for mtDNA in mouse germ cells. These results provide new information for mtDNA segregation models and for understanding the recurrence risks for mtDNA diseases.     

Mutations in EFHC1 cause juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.     

Larval stages of a living sea lily (stalked crinoid echinoderm)

The embryos and larvae of stalked crinoids, which are considered the most basal group of extant echinoderms, have not previously been described. In contrast, much is known about the development of the more accessible stalkless crinoids (feather stars), which are phylogenetically derived from stalked forms. Here we describe the development of a sea lily from fertilization to larval settlement. There are two successive larval stages: the first is a non-feeding auricularia stage with partly longitudinal ciliary bands (similar to the auricularia and bipinnaria larvae of holothurian and asteroid echinoderms, respectively); the second is a doliolaria larva with circumferential ciliary bands (similar to the earliest larval stage of stalkless crinoids). We suggest that a dipleurula-type larva is primitive for echinoderms and is the starting point for the evolution of additional larval forms within the phylum. From a wider evolutionary viewpoint, the demonstration that the most basal kind of echinoderm larva is a dipleurula is consistent with Garstang's auricularia theory for the phylogenetic origin of the chordate neural tube.