Faithful segregation of chromosomes during the first meiotic division requires that parental homologous kinetochores are physically connected until all pairs of homologous kinetochores attach to microtubules and orient toward opposite spindle poles during metaphase I 
. Crossovers (COs) in collaboration with sister chromatid cohesion provide these physical connections between maternal and paternal homologues in most organisms, including mammals 
. Each pair of homologues must have at least one (“obligate”) CO to ensure correct segregation during the first meiotic division.
COs are produced during the first meiotic prophase via recombination. A conserved enzyme, SPO11, introduces double strand breaks (DSBs) into the genome 
. DSBs can be repaired using either homologues (inter-homologue repair) or sister chromatids (inter-sister repair) as a recombination/repair template. To ensure CO formation, DSBs are preferentially repaired through the inter-homologue pathway, a phenomenon called the inter-homologue bias (IH bias) 
. This process also requires that homologous sequences recognise each other. The search for homology is aided by 3′ single-stranded overhangs of resected DSBs, which are produced at the beginning of the repair process 
. Two RecA homologs, RAD51 and DMC1, assist homology search by promoting strand invasion of resected DNA ends into homologous DNA sequences 
. The DSB repair process is also coordinated and tightly coupled with dynamic changes in chromatin architecture that facilitate the homology search and stabilise interactions between homologous DNA sequences 
One of the key events of meiotic chromosome dynamics is the formation of synaptonemal complexes (SCs) between pre-aligned homologues. SCs play an important role in DSB repair and CO formation 
. These proteinaceous structures consist of three parallel elongated elements, two axial elements (AEs) and a central element, which are linked by transverse filaments. The axial element comprises the shared axes of a sister chromatid pair. During SC formation, AEs of homologous chromosomes become connected via the central element/transverse filaments along their entire lengths. AEs begin to form during leptotene prior to the formation of SCs, which starts in zygotene. SCs are fully assembled during pachytene and disassemble as cells progress through diplotene.
SC dynamics and the DSB repair process are coordinated with progression in meiosis. In mammals, spermatocytes with defects in SC formation or DSB repair are eliminated at mid pachytene 
. Meiotic silencing of unsynapsed chromosomes (MSUC), in particular the silencing of sex chromosomes, is crucial for normal progression past this arrest point in males 
. Due to their restricted homology, X and Y chromosomes are only partially synapsed, and their unsynapsed regions are remodelled into a transcriptionally silenced, phospho-histone H2AX (γH2AX) rich chromatin domain, termed the sex body 
. Completion of SC formation on autosomes restricts MSUC to sex chromosomes, and is thus essential for full silencing of the X and Y 
. Spermatocytes with defective SCs exhibit increased expression from sex chromosomes, which is believed to trigger robust elimination by programmed cell death at mid pachytene 
. In budding yeast, where meiosis is most extensively explored, SC formation and DSB repair are also monitored by a meiotic prophase checkpoint 
A conserved feature of the mouse and budding yeast meiotic prophase checkpoints, is the involvement of ATM/ATR-like kinases 
. In mice, ATR is restricted to unsynapsed chromosome regions during zygotene and pachytene 
. Hence, ATR is assumed to phosphorylate H2AX in these regions, resulting in MSUC 
. In budding yeast, the ATR and ATM homologs, Mec1 and Tel1, respectively, are required for the prophase checkpoint in collaboration with Hop1, a meiosis-specific HORMA-domain protein (Ho
ev7 and MA
D2 homology domain) 
Hop1 is required for efficient DSB formation, SC formation and the prophase checkpoint 
. It also promotes IH bias by inhibiting DSB repair from sister chromatids. 
. In particular, phosphorylation of Hop1 by Tel1 and Mec1 is essential for the meiotic prophase checkpoint and for IH bias 
. Meiotic HORMA-domain proteins are evolutionarily conserved molecules, and they play crucial roles in chromosome behaviour (e.g., SC formation and DSB repair) in other organisms as well, including plants and nematodes 
. However, no prior studies have documented involvement of mammalian HORMA-domain proteins in any of the functions known for this important class of proteins.
In an effort to find genes that are specifically involved in meiotic chromosome behaviour in mice, we carried out a screen based on expression profiling of murine meiotic cells. This approach identified Hormad1 and Hormad2, two HORMA-domain encoding genes. HORMAD1 and HORMAD2 proteins are specifically expressed during meiosis in both sexes. We took advantage of characteristic features of mammalian meiosis and powerful cytological methods in mouse in order to better understand the relationships between mouse HORMADs, SC formation, DSB repair, and MSUC.