Behavior of aberrant chromosome configurations in Drosophila melanogaster female meiosis I.

One essential role of the first meiotic division is to reduce chromosome number by half. Although this is normally accomplished by segregating homologous chromosomes from each other, it is possible for a genome to have one or more chromosomes that lack a homolog (such as compound chromosomes), or have chromosomes with multiple potential homologs (such as in XXY females). These configurations complete meiosis but engage in unusual segregation patterns. In Drosophila melanogaster females carrying two compound chromosomes, the compounds can accurately segregate from each other, a process known as heterologous segregation. Similarly, in XXY females, when the X chromosomes fail to cross over, they often undergo secondary nondisjunction, where both Xs segregate away from the Y. Although both of these processes have been known for decades, the orientation mechanisms involved are poorly understood. Taking advantage of the recent discovery of chromosome congression in female meiosis I, we have examined a number of different aberrant chromosome configurations. We show that these genotypes complete congression normally, with their chromosomes bioriented at metaphase I arrest at the same rates that they segregate, indicating that orientation must be established during prometaphase I before congression. We also show that monovalent chromosomes can move out on the prometaphase I spindle, but the dot 4 chromosomes appear required for this movement. Finally, we show that, similar to achiasmate chromosomes, heterologous chromosomes can be connected by chromatin threads, suggesting a mechanism for how heterochromatic homology establishes these unusual biorientation patterns.

Light-activated serotonin for exploring its action in biological systems.

Serotonin (5-HT) is a neuromodulator involved in regulating mood, appetite, memory, learning, pain, and establishment of left-right (LR) asymmetry in embryonic development. To explore the role of 5-HT in physiology, we have created two forms of "caged" 5-HT, BHQ-O-5HT and BHQ-N-5HT. When exposed to 365 or 740 nm light, BHQ-O-5HT releases 5-HT through one- or two-photon excitation, respectively. BHQ-O-5HT mediated changes in neural activity in cultured mouse primary sensory neurons and the trigeminal ganglion and optic tectum of intact zebrafish larvae in the form of high-amplitude spiking in response to light. In Xenopus laevis embryos, light-activated 5-HT increased the occurrence of LR patterning defects. Maximal rates of LR defects were observed when 5-HT was released at stage 5 compared with stage 8. These experiments show the potential for BHQ-caged serotonins in studying 5-HT-regulated physiological processes.