INTRODUCTION Mechanisms underlying gametogenesis are complex and apparently divergent among metazoans. The DAZ (Deleted in Azoospermia) gene family provides one of the few lines of evidence that argue for evolutionary conservation of gametogenesis at the molecular level. DAZ family proteins

Mechanisms underlying gametogenesis are complex and apparently divergent among metazoans. The DAZ (Deleted in Azoospermia) gene family provides one of the few lines of evidence that argue for evolutionary conservation of gametogenesis at the molecular level. DAZ family proteins carry two conserved domains, namely the ribonucleoprotein (RNP)-type RNA recognition motif (RRM) and the DAZ motif, and have been found in both vertebrates and invertebrates (Cooke et al., 1996; Eberhart et al., 1996; Reijo et al., 1995). In humans, multiple copies of DAZ genes cluster in a small region on the Y chromosome (Reijo et al., 1995; Saxena et al., 1996). Deletion of the DAZ cluster has been correlated with azoospermia and oligospermia, which makes DAZ a strong candidate for the Azoospermia factor (AZF). In addition, an autosomal DAZ-like gene, termed DAZLA/DAZH, has been found on human chromosome 3 (Reijo et al., 1996; Seboun et al., 1997). Mouse carries Dazla, a homologue of DAZLA/DAZH, on an autosome, but has no DAZ cluster on the sex chromosome (Cooke et al., 1996). Hence, the human autosomal gene has been proposed to be the ancestor of the DAZ cluster, with its transposition to the Y chromosome during the evolution of primates (Saxena et al., 1996). Knock-out of mouse Dazla resulted in the complete absence of gamete production in both sexes (Ruggiu et al., 1997). In contrast, a homologue of DAZ in Drosophila, named boule, is essential for the meiotic progression in spermatogenesis but not in oogenesis (Eberhart et al., 1996). Expression of these DAZ family genes appears to be confined to the germline. Human DAZ and Drosophila boule are transcribed specifically in the male germline (Eberhart et al., 1996; Reijo et al., 1995; Saxena et al., 1996), while human DAZLA/DAZH and its mouse, zebrafish, and Xenopus homologues are expressed in the germline of both sexes (Houston et al., 1998; Maegawa et al., 1999; Ruggiu et al., 1997; Seligman and Page, 1998). The role of the DAZ family genes in the production of gametes is still largely unknown, partly due to the apparent phenotypic diversity caused by their defects. A human male missing the DAZ cluster shows a varying range of defects in spermatogenesis, from no germ cells at all to less severe spermatogenic arrest generating some mature spermatids (Reijo et al., 1995), indicating that the DAZ cluster is not absolutely necessary for the entry to meiosis and sperm differentiation. In the Dazla-defective mouse, female germ cells arrest at prophase of meiosis I, whereas male germ cells are affected at the proliferating stage (Ruggiu et al., 1997). In the Drosophila boule mutant, male germ cells arrest at the G2/M transition in meiosis I, exhibiting limited postmeiotic differentiation (Eberhart et al., 1996). This has been attributed 1069 Development 127, 1069-1079 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV3081