During C. elegans meiosis, the initial alignment between homologous chromosomes is structurally stabilized by the formation of the synaptonemal complex (SC) between them. Little is known, however, about the process of coordinating the assembly of SC components onto the chromosomes with the status of homolog alignment. We are investigating the function of
htp-1 and
htp-2, two paralogs of
him-3, a meiosis-specific chromosome core component required for homolog alignment and synapsis.
htp-1 and
htp-2 share high identity in both coding and non-coding sequences, however, the analysis of
htp-1(
gk174) null mutant and
htp-2(RNAi) phenotypes indicate that the two paralogs have non-redundant functions in meiosis.
htp-1 mutants exhibit a severe defect in the initial alignment of the autosomes, but not of the X chromosomes. However, DAPI staining at pachytene reveals typical parallel side-by-side arrangement of synapsed chromosomes, indicating the presence of extensive nonhomologous synapsis. In
htp-1 mutants the SC component SYP-1 is prematurely loaded on the chromosomes independently of the status of homolog alignment, suggesting that HTP-1 is required to prevent the association of SC components to chromosomes. Furthermore, recombination fails to initiate at wild-type level in
htp-1 mutants.
htp-2 depletion in
htp-1 mutant background does not modify the initial chromosome alignment defect of
htp-1 mutant but results in a lost of its stabilization. Furthermore at the onset of meiosis SYP-1 no longer associates with chromosomes but is localized to nuclear aggregates. Surprisingly however SYP-1 is loaded extensively on the unsynapsed chromosomes at later stages, suggesting a role for HTP-2 in the initiation of synapsis, rather than a requirement for the protein in loading SC components per se. Interestingly, we observe a partial rescue of recombination initiation when
htp-2 is depleted in
htp-1 mutant background, suggesting that the premature loading of SYP-1 and possibly other SC components- in
htp-1 mutant is the origin of its recombination defect. Together our results suggest that HTP-1 and HTP-2 play antagonistic roles at early prophase: HTP-1 is required for the prevention of non-homologous synapsis, whereas HTP-2 is required for synapsis initiation. Furthermore, we propose that premature loading of SC components to chromosomes may interfere with chromosome axis morphogenesis, thereby resulting in defects in chromosome alignment and initiation of recombination. Supported by CIHR and NSERC