C. elegans DAF-18/PTEN Mediates Nutrient-Dependent Arrest of Cell Cycle and Growth in the Germline

Masamitsu Fukuyama; Ann E. Rougvie; Joel H. Rothman

doi:10.1016/j.cub.2006.02.073

C. elegans DAF-18/PTEN Mediates Nutrient-Dependent Arrest of Cell Cycle and Growth in the Germline

Masamitsu Fukuyama, Ann E. Rougvie, Joel H. Rothman

Genetics, Cell Biology and Development (CBS)

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

146 Scopus citations

Abstract

The molecular pathways that link nutritional cues to developmental programs are poorly understood. Caenorhabditis elegans hatchlings arrest in a dormant state termed "L1 diapause" until food is supplied. However, little is known about what signal transduction pathways mediate nutritional status to control arrest and initiation of postembryonic development. We report that C. elegans embryonic germline precursors undergo G2 arrest with condensed chromosomes and remain arrested throughout L1 diapause. Loss of the DAF-18/PTEN tumor suppressor bypasses this arrest, resulting in inappropriate germline growth dependent on the AGE-1/PI-3 and AKT-1/PKB kinases. DAF-18 also regulates an insulin/IGF-like pathway essential for longevity and dauer larva formation. However, DAF-16/FoxO, which is repressed by this pathway, is not required for germline arrest in L1 diapause. Thus, these findings indicate that quiescence of germline development during L1 diapause is not a passive consequence of nutrient deprivation, but rather is actively maintained by DAF-18 through a pathway distinct from that which regulates longevity and dauer formation.

Original language	English (US)
Pages (from-to)	773-779
Number of pages	7
Journal	Current Biology
Volume	16
Issue number	8
DOIs	https://doi.org/10.1016/j.cub.2006.02.073
State	Published - Apr 18 2006

Bibliographical note

Funding Information:
We are grateful to C. Bargmann, Y. Bobbinec, J. Carlson, G. Gundersen, K. Kemphues, M. Maduro, G. Ruvkun, J. Schumacher, S. Strome, M. Yamashita, the C. elegans Genetic Center (CGC), and the C. elegans Knockout Consortium for valuable reagents and strains; M. Han, Y. Suzuki, R. Baugh, and P. Sternberg for sharing unpublished data; and members of the Rothman and Rougvie labs and the University of Minnesota Worm Community for discussion and encouragement. Some nematode strains were provided by the CGC, which is funded by the National Institutes of Health (NIH) National Center for Research Resources. M.F. was supported by a Postdoctoral Fellowship of the American Heart Association (AHA), Greater Midwest Affiliate during part of these studies. This work was supported by grants from the NIH (GM50227) and National Sciences Foundation (NSF) (IOB-0515682) to A.E.R. and the NIH (CA95943) and the March of Dimes Birth Defects Foundation to J.H.R.

Keywords

CELLCYCLE
DEVBIO
SIGNALING

Access

10.1016/j.cub.2006.02.073

OpenUrl availability

Full text

Cite this

@article{917c09c7444b40bdae38dba1ebd85c5b,

title = "C. elegans DAF-18/PTEN Mediates Nutrient-Dependent Arrest of Cell Cycle and Growth in the Germline",

abstract = "The molecular pathways that link nutritional cues to developmental programs are poorly understood. Caenorhabditis elegans hatchlings arrest in a dormant state termed {"}L1 diapause{"} until food is supplied. However, little is known about what signal transduction pathways mediate nutritional status to control arrest and initiation of postembryonic development. We report that C. elegans embryonic germline precursors undergo G2 arrest with condensed chromosomes and remain arrested throughout L1 diapause. Loss of the DAF-18/PTEN tumor suppressor bypasses this arrest, resulting in inappropriate germline growth dependent on the AGE-1/PI-3 and AKT-1/PKB kinases. DAF-18 also regulates an insulin/IGF-like pathway essential for longevity and dauer larva formation. However, DAF-16/FoxO, which is repressed by this pathway, is not required for germline arrest in L1 diapause. Thus, these findings indicate that quiescence of germline development during L1 diapause is not a passive consequence of nutrient deprivation, but rather is actively maintained by DAF-18 through a pathway distinct from that which regulates longevity and dauer formation.",

keywords = "CELLCYCLE, DEVBIO, SIGNALING",

author = "Masamitsu Fukuyama and Rougvie, {Ann E.} and Rothman, {Joel H.}",

note = "Funding Information: We are grateful to C. Bargmann, Y. Bobbinec, J. Carlson, G. Gundersen, K. Kemphues, M. Maduro, G. Ruvkun, J. Schumacher, S. Strome, M. Yamashita, the C. elegans Genetic Center (CGC), and the C. elegans Knockout Consortium for valuable reagents and strains; M. Han, Y. Suzuki, R. Baugh, and P. Sternberg for sharing unpublished data; and members of the Rothman and Rougvie labs and the University of Minnesota Worm Community for discussion and encouragement. Some nematode strains were provided by the CGC, which is funded by the National Institutes of Health (NIH) National Center for Research Resources. M.F. was supported by a Postdoctoral Fellowship of the American Heart Association (AHA), Greater Midwest Affiliate during part of these studies. This work was supported by grants from the NIH (GM50227) and National Sciences Foundation (NSF) (IOB-0515682) to A.E.R. and the NIH (CA95943) and the March of Dimes Birth Defects Foundation to J.H.R. ",

year = "2006",

month = apr,

day = "18",

doi = "10.1016/j.cub.2006.02.073",

language = "English (US)",

volume = "16",

pages = "773--779",

journal = "Current Biology",

issn = "0960-9822",

publisher = "Cell Press",

number = "8",

}

TY - JOUR

T1 - C. elegans DAF-18/PTEN Mediates Nutrient-Dependent Arrest of Cell Cycle and Growth in the Germline

AU - Fukuyama, Masamitsu

AU - Rougvie, Ann E.

AU - Rothman, Joel H.

N1 - Funding Information: We are grateful to C. Bargmann, Y. Bobbinec, J. Carlson, G. Gundersen, K. Kemphues, M. Maduro, G. Ruvkun, J. Schumacher, S. Strome, M. Yamashita, the C. elegans Genetic Center (CGC), and the C. elegans Knockout Consortium for valuable reagents and strains; M. Han, Y. Suzuki, R. Baugh, and P. Sternberg for sharing unpublished data; and members of the Rothman and Rougvie labs and the University of Minnesota Worm Community for discussion and encouragement. Some nematode strains were provided by the CGC, which is funded by the National Institutes of Health (NIH) National Center for Research Resources. M.F. was supported by a Postdoctoral Fellowship of the American Heart Association (AHA), Greater Midwest Affiliate during part of these studies. This work was supported by grants from the NIH (GM50227) and National Sciences Foundation (NSF) (IOB-0515682) to A.E.R. and the NIH (CA95943) and the March of Dimes Birth Defects Foundation to J.H.R.

PY - 2006/4/18

Y1 - 2006/4/18

N2 - The molecular pathways that link nutritional cues to developmental programs are poorly understood. Caenorhabditis elegans hatchlings arrest in a dormant state termed "L1 diapause" until food is supplied. However, little is known about what signal transduction pathways mediate nutritional status to control arrest and initiation of postembryonic development. We report that C. elegans embryonic germline precursors undergo G2 arrest with condensed chromosomes and remain arrested throughout L1 diapause. Loss of the DAF-18/PTEN tumor suppressor bypasses this arrest, resulting in inappropriate germline growth dependent on the AGE-1/PI-3 and AKT-1/PKB kinases. DAF-18 also regulates an insulin/IGF-like pathway essential for longevity and dauer larva formation. However, DAF-16/FoxO, which is repressed by this pathway, is not required for germline arrest in L1 diapause. Thus, these findings indicate that quiescence of germline development during L1 diapause is not a passive consequence of nutrient deprivation, but rather is actively maintained by DAF-18 through a pathway distinct from that which regulates longevity and dauer formation.

AB - The molecular pathways that link nutritional cues to developmental programs are poorly understood. Caenorhabditis elegans hatchlings arrest in a dormant state termed "L1 diapause" until food is supplied. However, little is known about what signal transduction pathways mediate nutritional status to control arrest and initiation of postembryonic development. We report that C. elegans embryonic germline precursors undergo G2 arrest with condensed chromosomes and remain arrested throughout L1 diapause. Loss of the DAF-18/PTEN tumor suppressor bypasses this arrest, resulting in inappropriate germline growth dependent on the AGE-1/PI-3 and AKT-1/PKB kinases. DAF-18 also regulates an insulin/IGF-like pathway essential for longevity and dauer larva formation. However, DAF-16/FoxO, which is repressed by this pathway, is not required for germline arrest in L1 diapause. Thus, these findings indicate that quiescence of germline development during L1 diapause is not a passive consequence of nutrient deprivation, but rather is actively maintained by DAF-18 through a pathway distinct from that which regulates longevity and dauer formation.

KW - CELLCYCLE

KW - DEVBIO

KW - SIGNALING

UR - http://www.scopus.com/inward/record.url?scp=33646063579&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646063579&partnerID=8YFLogxK

U2 - 10.1016/j.cub.2006.02.073

DO - 10.1016/j.cub.2006.02.073

M3 - Article

C2 - 16631584

AN - SCOPUS:33646063579

SN - 0960-9822

VL - 16

SP - 773

EP - 779

JO - Current Biology

JF - Current Biology

IS - 8

ER -

C. elegans DAF-18/PTEN Mediates Nutrient-Dependent Arrest of Cell Cycle and Growth in the Germline

Abstract

Bibliographical note

Keywords

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this