Temporal restriction to neural patterning

Temporal restriction to neural patterning - EMBRYONIC STEM...

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Embryonic Stem Cell-Derived Neural Progenitors Display Temporal Restriction to Neural Patterning ISABELLE A. BOUHON, a ALEXIS JOANNIDES, b HIDEMASA KATO, a SIDDHARTHAN CHANDRAN, b NICHOLAS D. ALLEN a,c a Neurobiology Programme, The Babraham Institute, Babraham, Cambridge, United Kingdom; b Cambridge Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom; c School of Biosciences, Cardiff University, Cardiff, United Kingdom Key Words. Embryonic stem cell • Neural differentiation • Patterning • Temporal restriction • Radial glia ABSTRACT Neural stem cells have considerable therapeutic potential be- cause of their ability to generate defined neuronal cell types for use in drug screening studies or cell-based therapies for neu- rodegenerative diseases. In this study, we differentiate mouse embryonic stem cells to neural progenitors with an initial forebrain identity in a defined system that enables systematic manipulation to generate more caudal fates, including mo- toneurons. We demonstrate that the ability to pattern embry- onic stem cell-derived neural progenitors is temporally re- stricted and show that the loss of responsiveness to morphogenetic cues correlates with constitutive expression of the basic helix-loop-helix transcription factors Olig2 and Mash1, epidermal growth factor receptor, and vimentin and parallels the onset of gliogenesis. We provide evidence for two temporal classes of embryonic stem cell-derived putative radial glia that coincide with a transition from neurogenesis to glio- genesis and a concomitant loss of regional identity. STEM CELLS 2006;24:1908–1913 INTRODUCTION The ability to generate defined neural cell types from embry- onic stem cells (ESCs) offers a powerful resource to study mechanisms of neural differentiation and fate specification. Application of such insights will, furthermore, be valuable for drug screening and cell-based repair strategies for a wide range of neurological disorders. Several studies have dem- onstrated the in vitro capacity of mouse ESCs to generate neurons [1–5], including regionally specified subtypes such as dopaminergic neurons and motoneurons (MNs) [6–8]. Generation of neural complexity is achieved through a process of morphogenetic development and tissue patterning [9–11]. This involves the induction and integration of signals from graded morphogens. Such signals function to establish regionally determined profiles of transcription factor gene expression that in turn specify distinct neural cell fates. A major principle of neural patterning is that cells exhibit spatially and temporally restricted competence to respond to patterning signals. Thus, forebrain neural progenitors may be progressively caudalized to acquire midbrain and then hind- brain and spinal characteristics. In this study we sought to predictably manipulate defined
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This note was uploaded on 09/29/2010 for the course BIOLOGY BISP 194 taught by Professor Hermann during the Fall '10 term at UCSD.

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Temporal restriction to neural patterning - EMBRYONIC STEM...

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