JAK/STATWords
--Somatic control of germline sexual development is mediated by the JAK/STAT pathway--
One of the world’s most important migrations ends in a place marked by no map: the gonad. This organ makes sperm and eggs, but it cannot perform this task- inherent to the success of sexual reproduction- unless germ cells first migrate to the gonad tissue, to receive the signals that will dictate their destiny as male or female. Despite the gonad’s role in shaping the sexual identity of germ cells, however, little is known about the molecular mechanisms underlaying this process. “For years, there has been this dance between somatic gonad cells and germ cells,” explained Johns Hopkins biology professor Mark Van Doren, “but we haven’t been able to identify the elements involved.”
Last July, however, Nature published a study in whichVan Doren and his colleagues identified one element- a “switch” for sexual identity. They demonstrated that in Drosophila, the JAK/STAT pathway- a cellular signaling route- mediates a critical signal from the male somatic gonad that is required for male germ cell development. In other words, no active JAK/STAT, no potential for a germ cell to become sperm.
Van Doren observed that STAT92E, a protein marker for JAK/STAT activity, was only expressed in male germ cells. This was the first tip that the pathway might play a unique role in male development. To confirm that presence of the STAT protein was due to JAK/STAT activation, however, Van Doren expressed a JAK inhibitor in his Drosophila. As expected, STAT92E expression was lost in the male germ cells. Interestingly, the presence of active JAK enabled germ cells – both male and female - to gain STAT protein expression. Female germ cells would normally not express STAT92E at all, leading Van Doren to his first conclusion:“The JAK/STAT pathway’s activity is necessary and sufficient for expression of STAT92E,” a protein seen in males.
But the JAK/STAT pathway is itself dependent on environmental factors for activation, as Van Doren observed. The pathway only “turned on” in germ cells that had completed their migration to the gonad. And just as contact with the gonad affected germ cell development, Van Doren found that sex of the gonad was influential, too. Normally female (XX) germ cells present in a masculinzed soma expressed the STAT92E protein characteristic of male germline development. Female germ cells also behaved uncharacteristcially in the presence of the JAK/STAT ligand, a binding molecule unique to the pathway. Typically, this molecule is expressed only in male gonads, reflecting that JAK/STAT activity (and all its components) is specific to males. When the ligand was expressed in female tissue, however, the female germ cells produced STAT like males would.
Male germ cell proliferation was also observed to be regulated by JAK/STAT acitivation, via the male gonad. Proliferation is specific to male germ cells during their early growth stages, but it was missing in male germ cells that lacked the somatic gonad. Additionally, female cells in a masculinzed soma proliferated early, as males would. This latter case could be problematic in an organism:“the sex of germ cells and the sex of the soma have to jive in order for sexual development to continue,” Van Doren explained. This understanding may provide rational for studies of drugs to help infertile couples.
Signals from the somatic gonad through JAK/STAT don’t act alone to influence malenss. Autonomous cues, like the male germline marker-1 (mgm-1), also play a part. On the whole, though, Van Doren’s study indicates that male germ cel development is first and foremost dependent upon non-autonomous cues via the JAK/STAT pathway. “But this isn’t the only pathway affecting the sex of germ cells,” Van Doren was careful to explain. And in the future, he hopes to identify additional somatic signals and germ cell autonomous cues that contribute to sexual development of the germline- the only means a species has to pass genetic cargo from one generation, to the next.
.MGW.
One of the world’s most important migrations ends in a place marked by no map: the gonad. This organ makes sperm and eggs, but it cannot perform this task- inherent to the success of sexual reproduction- unless germ cells first migrate to the gonad tissue, to receive the signals that will dictate their destiny as male or female. Despite the gonad’s role in shaping the sexual identity of germ cells, however, little is known about the molecular mechanisms underlaying this process. “For years, there has been this dance between somatic gonad cells and germ cells,” explained Johns Hopkins biology professor Mark Van Doren, “but we haven’t been able to identify the elements involved.”
Last July, however, Nature published a study in whichVan Doren and his colleagues identified one element- a “switch” for sexual identity. They demonstrated that in Drosophila, the JAK/STAT pathway- a cellular signaling route- mediates a critical signal from the male somatic gonad that is required for male germ cell development. In other words, no active JAK/STAT, no potential for a germ cell to become sperm.
Van Doren observed that STAT92E, a protein marker for JAK/STAT activity, was only expressed in male germ cells. This was the first tip that the pathway might play a unique role in male development. To confirm that presence of the STAT protein was due to JAK/STAT activation, however, Van Doren expressed a JAK inhibitor in his Drosophila. As expected, STAT92E expression was lost in the male germ cells. Interestingly, the presence of active JAK enabled germ cells – both male and female - to gain STAT protein expression. Female germ cells would normally not express STAT92E at all, leading Van Doren to his first conclusion:“The JAK/STAT pathway’s activity is necessary and sufficient for expression of STAT92E,” a protein seen in males.
But the JAK/STAT pathway is itself dependent on environmental factors for activation, as Van Doren observed. The pathway only “turned on” in germ cells that had completed their migration to the gonad. And just as contact with the gonad affected germ cell development, Van Doren found that sex of the gonad was influential, too. Normally female (XX) germ cells present in a masculinzed soma expressed the STAT92E protein characteristic of male germline development. Female germ cells also behaved uncharacteristcially in the presence of the JAK/STAT ligand, a binding molecule unique to the pathway. Typically, this molecule is expressed only in male gonads, reflecting that JAK/STAT activity (and all its components) is specific to males. When the ligand was expressed in female tissue, however, the female germ cells produced STAT like males would.
Male germ cell proliferation was also observed to be regulated by JAK/STAT acitivation, via the male gonad. Proliferation is specific to male germ cells during their early growth stages, but it was missing in male germ cells that lacked the somatic gonad. Additionally, female cells in a masculinzed soma proliferated early, as males would. This latter case could be problematic in an organism:“the sex of germ cells and the sex of the soma have to jive in order for sexual development to continue,” Van Doren explained. This understanding may provide rational for studies of drugs to help infertile couples.
Signals from the somatic gonad through JAK/STAT don’t act alone to influence malenss. Autonomous cues, like the male germline marker-1 (mgm-1), also play a part. On the whole, though, Van Doren’s study indicates that male germ cel development is first and foremost dependent upon non-autonomous cues via the JAK/STAT pathway. “But this isn’t the only pathway affecting the sex of germ cells,” Van Doren was careful to explain. And in the future, he hopes to identify additional somatic signals and germ cell autonomous cues that contribute to sexual development of the germline- the only means a species has to pass genetic cargo from one generation, to the next.
.MGW.
posted by Meagan G at
3:21 PM
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