P73 is an essential regulator of neural stem cell maintenance in embryonal and adult CNS neurogenesis

F. Talos; A. Abraham; A. V. Vaseva; L. Holembowski; S. E. Tsirka; A. Scheel; D. Bode; M. Dobbelstein; W. Brück; U. M. Moll

doi:10.1038/cdd.2010.131

P73 is an essential regulator of neural stem cell maintenance in embryonal and adult CNS neurogenesis

F. Talos, A. Abraham, A. V. Vaseva, L. Holembowski, S. E. Tsirka, A. Scheel, D. Bode, M. Dobbelstein, W. Brück, U. M. Moll

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

95 Scopus citations

Abstract

The p53 family member p73 is essential for brain development, but its precise role and scope remain unclear. Global p73 deficiency determines an overt and highly penetrant brain phenotype marked by cortical hypoplasia with ensuing hydrocephalus and hippocampal dysgenesis. The ΔNp73 isoform is known to function as a prosurvival factor of mature postmitotic neurons. In this study, we define a novel essential role of p73 in the regulation of the neural stem cell compartment. In both embryonic and adult neurogenesis, p73 has a critical role in maintaining an adequate neurogenic pool by promoting self-renewal and proliferation and inhibiting premature senescence of neural stem and early progenitor cells. Thus, products of the p73 gene locus are essential maintenance factors in the central nervous system, whose broad action stretches across the entire differentiation arch from stem cells to mature postmitotic neurons.

Original language	English (US)
Pages (from-to)	1816-1829
Number of pages	14
Journal	Cell Death and Differentiation
Volume	17
Issue number	12
DOIs	https://doi.org/10.1038/cdd.2010.131
State	Published - Dec 2010
Externally published	Yes

Keywords

adult neurogenesis
embryonic neurogenesis
neural stem cells
p73
p73 isoforms

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1038/cdd.2010.131

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title = "P73 is an essential regulator of neural stem cell maintenance in embryonal and adult CNS neurogenesis",

abstract = "The p53 family member p73 is essential for brain development, but its precise role and scope remain unclear. Global p73 deficiency determines an overt and highly penetrant brain phenotype marked by cortical hypoplasia with ensuing hydrocephalus and hippocampal dysgenesis. The ΔNp73 isoform is known to function as a prosurvival factor of mature postmitotic neurons. In this study, we define a novel essential role of p73 in the regulation of the neural stem cell compartment. In both embryonic and adult neurogenesis, p73 has a critical role in maintaining an adequate neurogenic pool by promoting self-renewal and proliferation and inhibiting premature senescence of neural stem and early progenitor cells. Thus, products of the p73 gene locus are essential maintenance factors in the central nervous system, whose broad action stretches across the entire differentiation arch from stem cells to mature postmitotic neurons.",

keywords = "adult neurogenesis, embryonic neurogenesis, neural stem cells, p73, p73 isoforms",

author = "F. Talos and A. Abraham and Vaseva, {A. V.} and L. Holembowski and Tsirka, {S. E.} and A. Scheel and D. Bode and M. Dobbelstein and W. Br{\"u}ck and Moll, {U. M.}",

note = "Funding Information: Acknowledgements. This work was funded by grants from the National Cancer Institute (CA93853 to UMM), Deutsche Krebshilfe (108173 to UMM) and NINDS (NS42168 to SET). We thank Frank McKeon for the p73 knockout mice and G Enikolopov for the Nestin–GFP mice. We thank B Anderson for the support with the behavioral tests.",

year = "2010",

month = dec,

doi = "10.1038/cdd.2010.131",

language = "English (US)",

volume = "17",

pages = "1816--1829",

journal = "Cell Death and Differentiation",

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AU - Talos, F.

AU - Abraham, A.

AU - Vaseva, A. V.

AU - Holembowski, L.

AU - Tsirka, S. E.

AU - Scheel, A.

AU - Bode, D.

AU - Dobbelstein, M.

AU - Brück, W.

AU - Moll, U. M.

N1 - Funding Information: Acknowledgements. This work was funded by grants from the National Cancer Institute (CA93853 to UMM), Deutsche Krebshilfe (108173 to UMM) and NINDS (NS42168 to SET). We thank Frank McKeon for the p73 knockout mice and G Enikolopov for the Nestin–GFP mice. We thank B Anderson for the support with the behavioral tests.

PY - 2010/12

Y1 - 2010/12

N2 - The p53 family member p73 is essential for brain development, but its precise role and scope remain unclear. Global p73 deficiency determines an overt and highly penetrant brain phenotype marked by cortical hypoplasia with ensuing hydrocephalus and hippocampal dysgenesis. The ΔNp73 isoform is known to function as a prosurvival factor of mature postmitotic neurons. In this study, we define a novel essential role of p73 in the regulation of the neural stem cell compartment. In both embryonic and adult neurogenesis, p73 has a critical role in maintaining an adequate neurogenic pool by promoting self-renewal and proliferation and inhibiting premature senescence of neural stem and early progenitor cells. Thus, products of the p73 gene locus are essential maintenance factors in the central nervous system, whose broad action stretches across the entire differentiation arch from stem cells to mature postmitotic neurons.

AB - The p53 family member p73 is essential for brain development, but its precise role and scope remain unclear. Global p73 deficiency determines an overt and highly penetrant brain phenotype marked by cortical hypoplasia with ensuing hydrocephalus and hippocampal dysgenesis. The ΔNp73 isoform is known to function as a prosurvival factor of mature postmitotic neurons. In this study, we define a novel essential role of p73 in the regulation of the neural stem cell compartment. In both embryonic and adult neurogenesis, p73 has a critical role in maintaining an adequate neurogenic pool by promoting self-renewal and proliferation and inhibiting premature senescence of neural stem and early progenitor cells. Thus, products of the p73 gene locus are essential maintenance factors in the central nervous system, whose broad action stretches across the entire differentiation arch from stem cells to mature postmitotic neurons.

KW - adult neurogenesis

KW - embryonic neurogenesis

KW - neural stem cells

KW - p73

KW - p73 isoforms

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P73 is an essential regulator of neural stem cell maintenance in embryonal and adult CNS neurogenesis

Abstract

Keywords

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