Keynote Conference - Interevent

Symp#7 Signaling in development
Chair Ricardo Guelerman Pinheiro Ramos
Ricardo Guelerman Pinheiro Ramos
University of São Paulo, Ribeirão Preto, Brazil
Introductory notes
Wnt Signaling, Stem Cells and Tissue Repair
Roel Nusse, Howard Hughes Medical Institute, Department of Developmental Biology, Lorry I. Lokey Stem Cell
Research Building. Stanford
Work from many laboratories has shown that Wnt signals are essential for the control over stem cells. A right balance
between the number of stem and differentiated cells is essential for the proper function of organs. Locally acting
signals, including Wnts, are important to maintain this balance in a spatially organized manner and these signals are
key to understanding the regulation of growth. How this is achieved is far from clear and is the subject of studies in our
lab, both in vivo and in cell culture. In vivo, a particular question we address is how physiological changes, such as
those occurring during hormonal stimuli, injury or programmed tissue degeneration have an impact on the selfrenewal
signals and on stem cell biology. Current research includes: 1) Identifying and tracing Wnt-responsive stem
cells in tissues; 2) mapping cis-acting transcriptional control elements (enhancers) that control Wnt gene expression in
normal and injured tissues; 3) the use of active Wnt proteins to maintain stem cells (including embryonic stem cells) in
cell culture; 4) presenting Wnt protein in a vectorial manner to stem cells to direct asymmetric cell division.
Formation of the Vertebrate Body Axis
Olivier Pourquié
Institut de genétique et biologie moleculaire et celulaire, INSERM, France
Hedgehog Signaling in Development and Disease
Matthew Scott
Departments of Developmental Biology, Genetics, and Bioengineering, Howard Hughes Medical Institute, Clark Center
West Wing W252, 318 Campus Drive, Stanford University School of Medicine, Stanford, California 94305-5439
Phone 650-725-7680 Fax (650) 725-2952
Hedgehog (Hh) signaling is important for the development of most organs and tissues. Damage to Hh signal
transduction components causes birth defects and cancer. We have been exploring four areas of Hedgehog signaling:
transduction in primary cilia, roles of Neuropilin proteins, identification of direct Hh target genes in the cerebellum and
medulloblastomas (MBs), and mutations in MB tumor genomes. Neuropilins 1 and 2 (Nrp1, 2) are transmembrane
proteins with roles in axon guidance and vascular endothelial growth factor (VEGF) signaling. We found that they are
important positive regulators of Hh signal transduction. Nrps are expressed at times and locations of active Hh signal
transduction during mouse development. We show that Nrps mediate Hh transduction between activated
Smoothened (Smo) protein and the negative regulator Suppressor of Fused (SuFu). Nrp1 transcription is induced by
Hh signaling and Nrp1 over-expression increases maximal Hh target gene activation, indicating the existence of a
positive feedback circuit. We are testing the importance of Nrps for growth of MB cells. Nrps act upstream of Gli
proteins, transcription factors that directly control Hh target gene transcription. We have identified direct targets of
Gli1 in normal mouse cerebellum development and in MBs, and found that Gli1 is located at some common genes in
the two cell types as well as many locations unique to each cell type. To understand better the properties of MB
tumor cells we are determining exome sequences of human and mouse tumors.
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