PgmNr Z6014: Positional cues within the nucleus underlie the dynamic chromosome events of meiosis in zebrafish.

Authors:
S. M. Burgess; Y. P. Blokhina; A. Nguyen; D. B. Chu; H. Roberts; T. A. Newman; B. W. Draper


Institutes
Univ California, Davis, Davis, CA.


Abstract:

Chromosome aneuploidy is a leading cause of birth defects and miscarriages in humans. The majority of aneuploidies are generated by errors in segregating homologous chromosomes at the first meiotic division. The incidence of chromosome segregation errors is higher in female mammals than males. Nonetheless, meiosis is largely understudied in females since the events of meiotic prophase I occur in the fetal ovary. The zebrafish model overcomes many of the limitations of using mice because gametogenesis occurs throughout adulthood in both sexes, the progeny number in the hundreds and embryos develop outside of the body. We will describe a comprehensive toolkit we have developed to study the chromosome events of meiotic prophase in zebrafish at the molecular, genetic and cellular levels. We found that both male and female zebrafish follows the canonical pathway of meiotic progression seen for fungi, plants, and mammals; that is, SPO11-induced double-strand breaks (DSB) are required for pairing and synapsis of homologous chromosomes. As seen for human males, synapsis (SYCP1 loading) initiates near telomeres and zippers inward until chromosomes are fully synapsed at pachytene. In zebrafish, the extension of the chromosome axis (SYCP3) also initiates near telomeres and extends just ahead synapsis.  There is a dramatic localization of DSBs (RAD51 foci) to the sites of clustered telomeres in the bouquet stage. Synapsed telomere regions are not always associated with RAD51 foci and many RAD51 foci are not associated with telomeres. These data suggest that multiple chromosomal loci undergoing DSB repair may coalesce to a single region of the nucleus during the earliest stages of pairing and synapsis and bring into question the mechanism of pairing.  Further analysis of the spo11 mutant shows that females are fertile, however, embryos are largely deformed due to high levels of aneuploidy; by contrast, spo11 males fail to make sperm.  While the meiotic program occurs until chromosome axes have formed, synapsis is absent. Together these findings point to zebrafish as an excellent model to study the dynamic events of meiotic prophase. Similarities and differences between multiple model organisms point to a conserved relationship between telomere clustering, DSB repair and synapsis initiation as contributing to the successful execution of the meiotic program.



ZFIN Genetics Index
1. spo11
2. SYCP1
3. SYCP3
4. RAD51