Section VIISex Determination in The Germ Line Versus the Soma

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The gene hierarchy that controls sex determination in the soma also controls sex determination in the germ line. In the germ line of males, the hierarchy directs spermatogenesis (see Schedl; L'Hernault; both this volume), whereas in the germ line of hermaphrodites, the hierarchy must first specify spermatogenesis and then switch to oogenesis (see Schedl; Anderson and Kimble; both this volume). Although there are major similarities between sex determination in the soma and in the germ line, these two processes differ in fundamental ways to allow each sex to specify the appropriate germ cell fate at the appropriate time: (1) The her, tra, and fem genes are essential for germ-line sex determination, but some of these genes ( tra-2 and fem-3 ) exhibit germ-line-specific regulation that differs in mechanism from their soma-specific regulation (Schedl; Anderson and Kimble; both this volume). (2) Germ-line sex determination requires genes not needed for somatic sex determination, the fog genes (feminization of the germ line) for spermatogenesis (Schedl and Kimble 1988; Barton and Kimble 1990; Ellis and Kimble 1995; Schedl, this volume) and the mog genes (masculinization of the germ line) for oogenesis (Graham and Kimble 1993; Graham et al. 1993; Schedl, this volume). (3) In the soma, tra-1 is a terminal switch gene whose product imposes the hermaphrodite pathway of differentiation, whereas in the germ line, this gene is not a switch gene (Hodgkin 1987a; Schedl et al. 1989). It participates in both female and male aspects of germ-line development. (4) The fem genes act at the terminal position in the gene hierarchy controlling germ-line sex determination (along with tra-1 , fog-1 , and fog-3 ). fem-3 acts as a germ-line switch gene: Active fem-3 triggers spermatogenesis and inactive fem-3 triggers oogenesis (Barton et al. 1987). The details of germ-line sex determination in males and hermaphrodites are reviewed by Schedl (this volume). The analysis presented below simply compares the roles of tra-1 and the fem genes in the soma versus the germ line.

In the soma, tra-1 is an XX-specific terminal switch gene that promotes hermaphrodite development. Male development ensues in XO animals because tra-1 is turned off by the fem genes and that is the only known role of the fem genes in the male soma. In the germ line, however, tra-1 functions in males to promote abundant spermatogenesis and block oogenesis; in its absence, small amounts of both sperm and oocytes are produced (Hodgkin 1987a; Schedl et al. 1989). Moreover, rather than simply acting to turn off tra-1 , the fem genes participate with tra-1 in promoting male development in the germ line. In so doing, the fem genes occupy a terminal position in the regulatory hierarchy. In the absence of FEM proteins, males produce only oocytes and do so even in the absence of tra-1 (Doniach and Hodgkin 1984; Hodgkin 1986). Hence, the block to oogenesis in wild-type males requires both the fem genes and tra-1 . Recall that in the soma, feminization by the loss of the fem genes is blocked by loss of tra-1 , one piece of evidence placing tra-1 downstream from the fem genes in that tissue type.

tra-1 also functions in the hermaphrodite germ line, but in the opposite capacity: to block spermatogenesis and promote abundant oogenesis, a role more in keeping with its somatic functions (Hodgkin 1987a; Schedl et al. 1989). Hence, with regard to its role in the germ line, it is more appropriate to think of tra-1 as playing an active but different part in XX and XO animals, rather than being functionally “on” in XX and “off” in XO animals, as it is in the soma. The following model for tra-1 germ-line functioning is consistent with known genetic and molecular data for this gene, but it departs from the conventional presentation of linear pathways and unifunctional elements. The basic idea is that in the germ line, tra-1 has opposite effects on germ cells that depend on its interactions with the fem genes. tra-1 promotes abundant spermatogenesis and blocks oogenesis when it interacts with (or is modified by) one or more of the fem genes, but in the absence of these interactions, it promotes abundant oogenesis and blocks spermatogenesis. tra-1 gain-of-function mutants rarely make sperm regardless of the activity state of the fem genes. This result can be rationalized by the view that the TRA-1 protein is refractory to interactions with the fem genes and hence constitutively functions in its female mode, only promoting oogenesis. A parallel situation may exist for fem-3 gain-of-function mutations. These alleles can fully masculinize the germ lines of either XX or XO animals independent of tra-1 . In the course of eliminating the normal controls on this gene, these dominant mutations appear to eliminate the need for the participation of tra-1 in the masculinizing activities of this gene.