Matches in SemOpenAlex for { <https://semopenalex.org/work/W2888492074> ?p ?o ?g. }
- W2888492074 abstract "Male fertility is dependent on spermatogonial stem cells (SSCs) that self-renew and produce differentiating germ cells. Growth factors produced within the testis are essential for SSC maintenance but intrinsic factors dictating SSC response to these stimuli poorly characterised. Here we studied the role of GILZ, a TSC22D family protein and spermatogenesis regulator, in spermatogonial function and signalling. While broadly expressed in the germline, GILZ was prominent in undifferentiated spermatogonia and Gilz deletion in adults resulted in exhaustion of the GFRα1+ SSC-containing population and germline degeneration. GILZ loss was associated with mTORC1 activation, suggesting enhanced growth factor signalling. Expression of deubiquitinase USP9X, an mTORC1 modulator required for spermatogenesis, was disrupted in Gilz mutants. Treatment with an mTOR inhibitor rescued GFRα1+ spermatogonial failure, indicating that GILZ-dependent mTORC1 inhibition is critical for SSC maintenance. Analysis of cultured undifferentiated spermatogonia lacking GILZ confirmed aberrant activation of ERK MAPK upstream mTORC1 plus USP9X downregulation and interaction of GILZ with TSC22D proteins. Our data indicate an essential role for GILZ-TSC22D complexes in ensuring appropriate response of undifferentiated spermatogonia to growth factors via distinct inputs to mTORC1." @default.
- W2888492074 created "2018-08-31" @default.
- W2888492074 creator A5006127122 @default.
- W2888492074 creator A5030821552 @default.
- W2888492074 creator A5033973134 @default.
- W2888492074 creator A5036855659 @default.
- W2888492074 creator A5047684342 @default.
- W2888492074 creator A5048961794 @default.
- W2888492074 creator A5064699406 @default.
- W2888492074 creator A5070848540 @default.
- W2888492074 creator A5087586345 @default.
- W2888492074 date "2018-01-01" @default.
- W2888492074 modified "2023-10-13" @default.
- W2888492074 title "GILZ-dependent modulation of mTORC1 regulates spermatogonial maintenance" @default.
- W2888492074 cites W1257374170 @default.
- W2888492074 cites W1831021874 @default.
- W2888492074 cites W1871909826 @default.
- W2888492074 cites W1897071795 @default.
- W2888492074 cites W1964204876 @default.
- W2888492074 cites W1968932167 @default.
- W2888492074 cites W1973839563 @default.
- W2888492074 cites W1975619619 @default.
- W2888492074 cites W1977000051 @default.
- W2888492074 cites W1977825177 @default.
- W2888492074 cites W1980440773 @default.
- W2888492074 cites W1982166284 @default.
- W2888492074 cites W1986896225 @default.
- W2888492074 cites W1997919787 @default.
- W2888492074 cites W1998931389 @default.
- W2888492074 cites W1999865455 @default.
- W2888492074 cites W2000761601 @default.
- W2888492074 cites W2003819643 @default.
- W2888492074 cites W2006321057 @default.
- W2888492074 cites W2009801071 @default.
- W2888492074 cites W2014657344 @default.
- W2888492074 cites W2015292331 @default.
- W2888492074 cites W2016869069 @default.
- W2888492074 cites W2016903743 @default.
- W2888492074 cites W2018508671 @default.
- W2888492074 cites W2022672527 @default.
- W2888492074 cites W2025000087 @default.
- W2888492074 cites W2027568735 @default.
- W2888492074 cites W2032997568 @default.
- W2888492074 cites W2040104847 @default.
- W2888492074 cites W2041784242 @default.
- W2888492074 cites W2042202436 @default.
- W2888492074 cites W2043851579 @default.
- W2888492074 cites W2044213811 @default.
- W2888492074 cites W2044512117 @default.
- W2888492074 cites W2050075369 @default.
- W2888492074 cites W2050111991 @default.
- W2888492074 cites W2055120349 @default.
- W2888492074 cites W2057322816 @default.
- W2888492074 cites W2063861465 @default.
- W2888492074 cites W2064936324 @default.
- W2888492074 cites W2065914616 @default.
- W2888492074 cites W2073738799 @default.
- W2888492074 cites W2075234503 @default.
- W2888492074 cites W2076763303 @default.
- W2888492074 cites W2078708536 @default.
- W2888492074 cites W2081005510 @default.
- W2888492074 cites W2083640512 @default.
- W2888492074 cites W2085171607 @default.
- W2888492074 cites W2085950149 @default.
- W2888492074 cites W2087669700 @default.
- W2888492074 cites W2088612857 @default.
- W2888492074 cites W2094399892 @default.
- W2888492074 cites W2098912234 @default.
- W2888492074 cites W2099930565 @default.
- W2888492074 cites W2100701743 @default.
- W2888492074 cites W2101565743 @default.
- W2888492074 cites W2105036071 @default.
- W2888492074 cites W2110804359 @default.
- W2888492074 cites W2111352469 @default.
- W2888492074 cites W2111705682 @default.
- W2888492074 cites W2117239824 @default.
- W2888492074 cites W2119593016 @default.
- W2888492074 cites W2126768340 @default.
- W2888492074 cites W2127063807 @default.
- W2888492074 cites W2129829048 @default.
- W2888492074 cites W2134106182 @default.
- W2888492074 cites W2136272779 @default.
- W2888492074 cites W2142839629 @default.
- W2888492074 cites W2145883703 @default.
- W2888492074 cites W2150552014 @default.
- W2888492074 cites W2150582941 @default.
- W2888492074 cites W2154853638 @default.
- W2888492074 cites W2163996125 @default.
- W2888492074 cites W2171727209 @default.
- W2888492074 cites W2223549218 @default.
- W2888492074 cites W2261527367 @default.
- W2888492074 cites W2322395793 @default.
- W2888492074 cites W2334391200 @default.
- W2888492074 cites W2406347364 @default.
- W2888492074 cites W2416544067 @default.
- W2888492074 cites W2510110480 @default.
- W2888492074 cites W2536166319 @default.
- W2888492074 cites W2548044639 @default.
- W2888492074 cites W2575297515 @default.
- W2888492074 cites W2586656349 @default.