TY - JOUR
T1 - Dedifferentiation of primary spermatocytes into germ cell tumors in C. elegans Lacking the pumilio-like protein PUF-8
AU - Subramaniam, Kuppuswamy
AU - Seydoux, Geraldine
N1 - Funding Information:
In puf-8 mutants, 1° spermatocytes dedifferentiate into mitotically cycling germ cells, as evidenced by the loss of spermatogenesis markers (MO and MSP), the return of early germ cell markers (P granules and GLP-1), and reentry into mitosis and tumor formation. We do not yet know how 1° spermatocytes transition from metaphase of meiosis I to mitosis, but one possibility is that sister chromatid cohesion fails, causing at least some cells to undergo a division that is more akin to an equational division (meiosis II) than a reductional division (meiosis I). This possibility is supported by the high frequency of aneuploidy in puf-8 mutants grown at 20°C, and by the equational segregation of the X in XO tumors. A return to mitosis by cells that initiate but fail to complete the meiotic program has also been observed in gld-1 mutants. GLD-1 is an RNA binding protein required for progression through meiotic prophase [19] . In the absence of gld-1 , germ cells exit meiosis during pachytene (prophase of meiosis I) and return to mitosis, resulting in a tumorous germline. Unlike puf-8 mutants, gld-1 germ cells never complete meiotic prophase and do not initiate gametogenesis. Furthermore, whereas puf-8 affects only cells undergoing spermatogenesis, gld-1 affects only cells destined to become oocytes. These differences notwithstanding, in both the gld-1 and puf-8 mutants, failure to complete meiosis is linked to tumor formation. In humans, germline tumors are most commonly thought to be derived from premeiotic germ cells. An exception, however, may exist in the male germline. Spermatocytic seminomas are testicular tumors derived from germ cells that have initiated spermatogenesis and may also have initiated meiosis, although this last point is still under debate [32, 33] . Our findings demonstrate that cells that have progressed past meiotic prophase can give rise to tumors, and they raise the possibility that PUF proteins could function as tumor suppressors in the germlines of other organisms.
PY - 2003/1/21
Y1 - 2003/1/21
N2 - PUF proteins are a conserved family of RNA binding proteins that regulate RNA stability and translation by binding to specific sequences in 3′-untranslated regions. Drosophila PUMILIO and C. elegans FBF are essential for self-renewal of germline stem cells, suggesting that a common function of PUF proteins may be to sustain mitotic proliferation of stem cells [1]. Here, we show that PUF-8, the C. elegans PUF most related to PUMILIO, performs a different function in germ cells that have begun meiosis: in primary spermatocytes, puf-8 is required to maintain meiosis and prevent the return to mitosis. Primary spermatocytes lacking PUF-8 complete meiotic prophase but do not undergo normal meiotic divisions. Instead, they dedifferentiate back into mitotically cycling germ cells and form rapidly growing tumors. These findings reveal an unexpected ability for germ cells that have completed meiotic prophase to return to the mitotic cycle, and they support the view that PUF proteins regulate multiple transitions during germline development.
AB - PUF proteins are a conserved family of RNA binding proteins that regulate RNA stability and translation by binding to specific sequences in 3′-untranslated regions. Drosophila PUMILIO and C. elegans FBF are essential for self-renewal of germline stem cells, suggesting that a common function of PUF proteins may be to sustain mitotic proliferation of stem cells [1]. Here, we show that PUF-8, the C. elegans PUF most related to PUMILIO, performs a different function in germ cells that have begun meiosis: in primary spermatocytes, puf-8 is required to maintain meiosis and prevent the return to mitosis. Primary spermatocytes lacking PUF-8 complete meiotic prophase but do not undergo normal meiotic divisions. Instead, they dedifferentiate back into mitotically cycling germ cells and form rapidly growing tumors. These findings reveal an unexpected ability for germ cells that have completed meiotic prophase to return to the mitotic cycle, and they support the view that PUF proteins regulate multiple transitions during germline development.
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U2 - 10.1016/S0960-9822(03)00005-8
DO - 10.1016/S0960-9822(03)00005-8
M3 - Article
C2 - 12546787
AN - SCOPUS:0037458114
SN - 0960-9822
VL - 13
SP - 134
EP - 139
JO - Current Biology
JF - Current Biology
IS - 2
ER -