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Company of Biologists Workshop – Growth, Division and Differentiation – Day 1

Posted by , on 19 September 2011

In the series of The Company of Biologists Workshops a select group of roughly 30 scientists have gathered at Wiston House, West Sussex, UK, from September 18 to 21, 2011, to discuss the topic of “Growth, division and differentiation: Understanding Developmental Control”. This workshop series aims at fostering collaboration and conceptual advancement by bringing together researchers from various backgrounds and by facilitating close scientific exchange and cross-pollination to tackle challenges in current biological research.

We are a group of workshop participants – PhD students, postdocs and lab heads – who will be updating the Node with collectively written posts from the meeting. All speakers have approved the text before it was posted.

The scientific program of the opening afternoon session on Sept. 18 included a series of four excellent plenary talks followed by an evening poster session.

Ludger Hengst from Innsbruck Medical University (Austria) opened up with a talk elucidating the role of the CDK inhibitor p27, specifically its regulation by growth factor-related signaling molecules such as JAK2, exemplifying how tyrosine kinase signals can directly modulate cell cycle regulators and underlining the immediate clinical relevance, for example, in the context of JAK2 mutations in proliferative diseases such as polycythemia vera.

Jackie Lees from MIT presented work on the role of the Rb tumor suppressor in fate commitment and cancer. To elucidate tissue tropism and heterogeneity of Rb-associated tumors (here: osteosarcoma) this work exploited Rb-/-, p53-/- as well as Rb/p53 double mutants in Osterix-positive bone precursor cells [see Calo et al., 2010]. In an E2F-independent mechanism, Rb appears to potentiate Runx2 serving as an activator in osteogenesis. While Rb mutants did show surprisingly little effect, the combined Rb/p53 deletions not only lead to blockage of differentiation at the pre-osteoblast stage, but to a reversion toward even earlier stages, enabling this earlier stage mesenchymal precursor to give rise to an extended spectrum of derivatives including brown fat tissue tumors (hibernoma). Re-introduction of Rb reinstated terminal bone differentiation. This work also illustrated how the heterogeneity of tumors could arise from the dedifferentiation of more mature stages, so that tumors may contain cells with stem cell character without necessarily having arisen from a “cancer stem cell”.

While Ludger Hengst’s earlier presentation had primarily drawn attention to N-terminal interaction partners of p27 during late G1, the next talk by P. Renee Yew from the University of Texas focused on its C-terminal regulatory interaction. To this end, the work presented here introduced the Xenopus inhibitor of CDKs Xic1 (exhibiting both p21 and p27 features) and showed novel regulatory interactions with PCNA during S-phase of the cell cycle.

Peter Sicinski, Harvard Medical School, presented data on a cell cycle regulation-independent role of Cyclin-E on CDK5 in the generation and functionality of neuronal synapses and demonstrated its relevance for cognitive behavior in mouse models. In this context, CDK5 appears to partner with p35 and p39 to execute its essential function in neuronal differentiation and synaptogenesis. On the other hand, formation of a cytosolic complex with Cyclin-E and p27 appears to render it inactive and profoundly interferes with synapse formation and learning.

This concluded the first day’s session of oral presentations. A common thread were the identification of novel linkages between classic cell cycle machinery and a range of signaling pathways involved in the control of differentiation. So inspired, ample discussion continued throughout the evening poster session and beyond.

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