The proto-oncogene Ret is required for male foetal germ cell survival

Denise Miles; Jocelyn van den Bergen; Stephanie Wakeling; Richard Anderson; Andrew Sinclair; Patrick Western

doi:10.1016/j.ydbio.2012.02.014

The proto-oncogene Ret is required for male foetal germ cell survival

Denise Miles, Jocelyn van den Bergen, Stephanie Wakeling, Richard Anderson, Andrew Sinclair, Patrick Western

Research output: Contribution to journal › Article › Research › peer-review

13 Citations (Scopus)

Abstract

The spermatogenic and oogenic lineages originate from bipotential primordial germ cells in response to signalling in the foetal testis or ovary, respectively. The signals required for male germ cell commitment and their entry into mitotic arrest remain largely unknown. Recent data show that the ligand GDNF is up regulated in the foetal testis indicating that it may be involved in male germ cell development. In this study genetic analysis of GDNF-RET signalling shows that RET is required for germ cell survival. Affected germ cells in Ret-/- mice lose expression of key germ cell markers, abnormally express cell cycle markers and undergo apoptosis. Surprisingly, a similar phenotype was not detected in Gdnf-/- mice indicating that either redundancy with a Gdnf related gene might compensate for its loss, or that RET operates in a GDNF independent manner in mouse foetal germ cells. Either way, this study identifies the proto-oncogene RET as a novel component of the foetal male germ cell development pathway.

Original language	English
Pages (from-to)	101 - 109
Number of pages	9
Journal	Developmental Biology
Volume	365
Issue number	1
DOIs	https://doi.org/10.1016/j.ydbio.2012.02.014
Publication status	Published - 2012

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Cite this

@article{7bdf8cd1e4bd42979012a88aefea7f40,

title = "The proto-oncogene Ret is required for male foetal germ cell survival",

abstract = "The spermatogenic and oogenic lineages originate from bipotential primordial germ cells in response to signalling in the foetal testis or ovary, respectively. The signals required for male germ cell commitment and their entry into mitotic arrest remain largely unknown. Recent data show that the ligand GDNF is up regulated in the foetal testis indicating that it may be involved in male germ cell development. In this study genetic analysis of GDNF-RET signalling shows that RET is required for germ cell survival. Affected germ cells in Ret-/- mice lose expression of key germ cell markers, abnormally express cell cycle markers and undergo apoptosis. Surprisingly, a similar phenotype was not detected in Gdnf-/- mice indicating that either redundancy with a Gdnf related gene might compensate for its loss, or that RET operates in a GDNF independent manner in mouse foetal germ cells. Either way, this study identifies the proto-oncogene RET as a novel component of the foetal male germ cell development pathway.",

author = "Denise Miles and {van den Bergen}, Jocelyn and Stephanie Wakeling and Richard Anderson and Andrew Sinclair and Patrick Western",

year = "2012",

doi = "10.1016/j.ydbio.2012.02.014",

language = "English",

volume = "365",

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journal = "Developmental Biology",

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TY - JOUR

T1 - The proto-oncogene Ret is required for male foetal germ cell survival

AU - Miles, Denise

AU - van den Bergen, Jocelyn

AU - Wakeling, Stephanie

AU - Anderson, Richard

AU - Sinclair, Andrew

AU - Western, Patrick

PY - 2012

Y1 - 2012

N2 - The spermatogenic and oogenic lineages originate from bipotential primordial germ cells in response to signalling in the foetal testis or ovary, respectively. The signals required for male germ cell commitment and their entry into mitotic arrest remain largely unknown. Recent data show that the ligand GDNF is up regulated in the foetal testis indicating that it may be involved in male germ cell development. In this study genetic analysis of GDNF-RET signalling shows that RET is required for germ cell survival. Affected germ cells in Ret-/- mice lose expression of key germ cell markers, abnormally express cell cycle markers and undergo apoptosis. Surprisingly, a similar phenotype was not detected in Gdnf-/- mice indicating that either redundancy with a Gdnf related gene might compensate for its loss, or that RET operates in a GDNF independent manner in mouse foetal germ cells. Either way, this study identifies the proto-oncogene RET as a novel component of the foetal male germ cell development pathway.

AB - The spermatogenic and oogenic lineages originate from bipotential primordial germ cells in response to signalling in the foetal testis or ovary, respectively. The signals required for male germ cell commitment and their entry into mitotic arrest remain largely unknown. Recent data show that the ligand GDNF is up regulated in the foetal testis indicating that it may be involved in male germ cell development. In this study genetic analysis of GDNF-RET signalling shows that RET is required for germ cell survival. Affected germ cells in Ret-/- mice lose expression of key germ cell markers, abnormally express cell cycle markers and undergo apoptosis. Surprisingly, a similar phenotype was not detected in Gdnf-/- mice indicating that either redundancy with a Gdnf related gene might compensate for its loss, or that RET operates in a GDNF independent manner in mouse foetal germ cells. Either way, this study identifies the proto-oncogene RET as a novel component of the foetal male germ cell development pathway.

UR - http://www.sciencedirect.com/science/article/pii/S0012160612000838

U2 - 10.1016/j.ydbio.2012.02.014

DO - 10.1016/j.ydbio.2012.02.014

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JO - Developmental Biology

JF - Developmental Biology

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