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Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling.
Dis Model Mech 2008 Sep-Oct; 1(2-3):131-43; discussion 141DM

Abstract

We have identified two genes, Smed-PTEN-1 and Smed-PTEN-2, capable of regulating stem cell function in the planarian Schmidtea mediterranea. Both genes encode proteins homologous to the mammalian tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Inactivation of Smed-PTEN-1 and -2 by RNA interference (RNAi) in planarians disrupts regeneration, and leads to abnormal outgrowths in both cut and uncut animals followed soon after by death (lysis). The resulting phenotype is characterized by hyperproliferation of neoblasts (planarian stem cells), tissue disorganization and a significant accumulation of postmitotic cells with impaired differentiation capacity. Further analyses revealed that rapamycin selectively prevented such accumulation without affecting the normal neoblast proliferation associated with physiological turnover and regeneration. In animals in which PTEN function is abrogated, we also detected a significant increase in the number of cells expressing the planarian Akt gene homolog (Smed-Akt). However, functional abrogation of Smed-Akt in Smed-PTEN RNAi-treated animals does not prevent cell overproliferation and lethality, indicating that functional abrogation of Smed-PTEN is sufficient to induce abnormal outgrowths. Altogether, our data reveal roles for PTEN in the regulation of planarian stem cells that are strikingly conserved to mammalian models. In addition, our results implicate this protein in the control of stem cell maintenance during the regeneration of complex structures in planarians.

Authors+Show Affiliations

Center for Regenerative and Developmental Biology, Forsyth Institute, and Developmental Biology Department, Harvard School of Dental Medicine, Boston, MA 02115, USA. noviedo@drmichaellevin.orgNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

19048075

Citation

Oviedo, Néstor J., et al. "Planarian PTEN Homologs Regulate Stem Cells and Regeneration Through TOR Signaling." Disease Models & Mechanisms, vol. 1, no. 2-3, 2008, pp. 131-43; discussion 141.
Oviedo NJ, Pearson BJ, Levin M, et al. Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling. Dis Model Mech. 2008;1(2-3):131-43; discussion 141.
Oviedo, N. J., Pearson, B. J., Levin, M., & Sánchez Alvarado, A. (2008). Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling. Disease Models & Mechanisms, 1(2-3), pp. 131-43; discussion 141. doi:10.1242/dmm.000117.
Oviedo NJ, et al. Planarian PTEN Homologs Regulate Stem Cells and Regeneration Through TOR Signaling. Dis Model Mech. 2008;1(2-3):131-43; discussion 141. PubMed PMID: 19048075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling. AU - Oviedo,Néstor J, AU - Pearson,Bret J, AU - Levin,Michael, AU - Sánchez Alvarado,Alejandro, Y1 - 2008/09/18/ PY - 2008/01/09/received PY - 2008/03/29/accepted PY - 2008/12/3/pubmed PY - 2009/4/15/medline PY - 2008/12/3/entrez SP - 131-43; discussion 141 JF - Disease models & mechanisms JO - Dis Model Mech VL - 1 IS - 2-3 N2 - We have identified two genes, Smed-PTEN-1 and Smed-PTEN-2, capable of regulating stem cell function in the planarian Schmidtea mediterranea. Both genes encode proteins homologous to the mammalian tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Inactivation of Smed-PTEN-1 and -2 by RNA interference (RNAi) in planarians disrupts regeneration, and leads to abnormal outgrowths in both cut and uncut animals followed soon after by death (lysis). The resulting phenotype is characterized by hyperproliferation of neoblasts (planarian stem cells), tissue disorganization and a significant accumulation of postmitotic cells with impaired differentiation capacity. Further analyses revealed that rapamycin selectively prevented such accumulation without affecting the normal neoblast proliferation associated with physiological turnover and regeneration. In animals in which PTEN function is abrogated, we also detected a significant increase in the number of cells expressing the planarian Akt gene homolog (Smed-Akt). However, functional abrogation of Smed-Akt in Smed-PTEN RNAi-treated animals does not prevent cell overproliferation and lethality, indicating that functional abrogation of Smed-PTEN is sufficient to induce abnormal outgrowths. Altogether, our data reveal roles for PTEN in the regulation of planarian stem cells that are strikingly conserved to mammalian models. In addition, our results implicate this protein in the control of stem cell maintenance during the regeneration of complex structures in planarians. SN - 1754-8411 UR - https://www.unboundmedicine.com/medline/citation/19048075/Planarian_PTEN_homologs_regulate_stem_cells_and_regeneration_through_TOR_signaling_ L2 - http://dmm.biologists.org/cgi/pmidlookup?view=long&pmid=19048075 DB - PRIME DP - Unbound Medicine ER -