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Poster<br />

505. Cell Lineage <strong>an</strong>d Cell Fate Specification<br />

Location: South Hall A<br />

Time: Tuesday, October 20, <strong>2009</strong>, 8:00 am - 12:00 noon<br />

Program#/Poster#: 505.4/A4<br />

Topic: A.02.b. Cell lineage <strong>an</strong>d cell fate specification<br />

Title: Coordinated control of self-renewal <strong>an</strong>d differentiation of neural stem cells by Myc <strong>an</strong>d<br />

<strong>the</strong> p19ARF-p53 pathway<br />

Authors: *M. NAKAFUKU 1 , M. NAGAO 1 , K. CAMPBELL 1 , K. BURNS 1 , C.-Y. KUAN 1 , A.<br />

TRUMPP 2 ;<br />

1 Cincinnati Children's Hosp. Med. Ctr., Cincinnati, OH; 2 Deutsches Krebs<strong>for</strong>schungszentrum<br />

(DKFZ), DKFZ-ZMBH Alli<strong>an</strong>ce, Heidelberg, Germ<strong>an</strong>y<br />

Abstract: The modes of proliferation <strong>an</strong>d differentiation of neural stem cells (NSCs) are<br />

coordinately controlled during development, but <strong>the</strong> underlying mech<strong>an</strong>isms remain largely<br />

unknown. Here we provide evidence that <strong>the</strong> protooncoprotein Myc <strong>an</strong>d <strong>the</strong> tumor suppressor<br />

p19ARF regulate both NSC self-renewal <strong>an</strong>d <strong>the</strong>ir neuronal <strong>an</strong>d glial fate in a developmental<br />

stage-dependent m<strong>an</strong>ner. Early-stage NSCs have low p19ARF expression <strong>an</strong>d retain a high selfrenewal<br />

<strong>an</strong>d neurogenic capacity, whereas late-stage NSCs with higher p19ARF expression<br />

possess a lower self-renewal capacity <strong>an</strong>d predomin<strong>an</strong>tly generate glia. Overexpression of Myc<br />

or inactivation of p19ARF reverts <strong>the</strong> properties of late-stage NSCs to those of early-stage cells.<br />

Conversely, inactivation of Myc or <strong>for</strong>ced p19ARF expression attenuates self-renewal <strong>an</strong>d<br />

induces precocious gliogenesis through modulation of <strong>the</strong> responsiveness to STAT3-mediated<br />

gliogenic signals. These actions of p19ARF in NSCs are mainly mediated by p53. We propose<br />

that opposing actions of Myc <strong>an</strong>d <strong>the</strong> p19ARF-p53 pathway have import<strong>an</strong>t functions in<br />

coordinated developmental control of self-renewal <strong>an</strong>d neuronal <strong>an</strong>d glial fate choices in NSCs.<br />

Disclosures: M. Nakafuku, None; M. Nagao, None; K. Campbell, None; K. Burns, None; C.<br />

Ku<strong>an</strong>, None; A. Trumpp, None.<br />

Poster<br />

505. Cell Lineage <strong>an</strong>d Cell Fate Specification<br />

Location: South Hall A

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