Nadia Dahmane , Ph.D.

Assistant Professor
Molecular and Cellular Oncogenesis Program
215-495-6840, Office
ndahmane@wistar.org

Introduction

Research in the Dahmane lab aims at understanding the mechanisms by which the Sonic hedgehog gene operates during normal nervous system development and in certain brain tumors, particularly medulloblastomas.

Research Summary

Patterning and growth constitute two critical aspects of brain development that must be coordinately regulated. Important intercellular signaling pathways involved in this coordination include those activated by the Hedgehog genes, Fibroblast Growth Factors (FGFs), and Bone Morphogenetic Proteins (BMPs). Sonic hedgehog (SHH) initially secreted from midline mesodermal cells (and later from ventral floor plate cells in posterior regions) induces correct dorso-ventral (D/V) regionalization in the central nervous system (CNS) leading to the differentiation of ventral cell types along the entire neuraxis. In contrast to this early period, later during embryogenesis and postnatal stages, SHH is required for proliferation of precursor cells in dorsal brain regions, notably in the cerebellum and neocortex. The loss of SHH signaling in the early mesoderm and neural tube leads to holoprosencephaly and cyclopia, while excess signaling can induce tumors, such as medulloblastoma of the cerebellum. A tight regulation of this signaling pathway is thus critical not only for normal development but also during adulthood for homeostasis in many organs in addition to the CNS, for stem cell behavior and to prevent tumor formation.

Selected Publications

Gitton, Y.*, Dahmane, N.*, Baik, S., Ruiz i Altaba, A. Neidhardt, L.*, Scholze, M., Hermann, B., Kahlem, P.*, Kahla, A.*, Schrinner, S., yildirimman, R., Herwig, R., Legach, H. and Yaspo, M.L. (2002) A multilevel gene expression analysis of human chromosome 21 orthologs in the mouse: potential insights into Down Syndrome. Nature, 420: 586-590

Ruiz i Altaba A., Sanchez, P, Dahmane, N. (2002) Gli and Hedgehog in Cancer: Tumors, embryos and stem cells. Nat Rev Cancer 2: 361-372.

Ruiz i Altaba, A., Palmer, V., Dahmane, N. (2002) Hedgehog-Gli signaling and the growth of the brain. Nat Rev Neurosci. 1: 24-33.