The topographic projection of each thalamic nucleus to a unique set of cortical areas underlies the input specificity characterizing each sensory modality. Although the importance of the patterning of thalamocortical projections for normal brain function has long been appreciated, the underlying developmental mechanisms remain largely unknown.
The aim of this project is to identify the key molecular cues patterning thalamocortical projections in mammals. We recently obtained evidence demonstrating that (i) topographic cues present in an intermediate target, the ventral telencephalon, play a critical role in the sorting of thalamocortical projections to distinct cortical domains and (ii) that the bHLH transcription factor Neurogenin2 specifies cell-autonomously the topography of thalamic projections by controlling axon responsiveness to the intermediate cues present in the ventral telencephalon. Based on these preliminary results, the following Specific Aims will be carried out: 1. Determine the role of the ventral telencephalon in the patterning of thalamic axons projections to distinct cortical domains using a new 'whole-mount' in vitro assay recapitulating some of the key aspects of the topography of thalamic axon projections observed in vivo. 2. Determine the role of Neurogenin2 in the specification of the topography of thalamocortical projection. We will test the spatial and temporal requirement of Ngn2 expression in the specification of thalamic neurons connectivity using a gain-of-function approach where full-length Ngn2 or interfering constructs will be ectopically or heterochronically expressed in the dorsal thalamus using an electroporation-mediated gene transfer. 3. Isolate and characterize the transcriptional targets of Neurogenin2 in the developing thalamus. We will identify the set of genes controlled transcriptionally by Ngn2 and involved in the patterning of thalamic axon projections using both a candidate approach and an unbiased genome-wide approach.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS047701-05
Application #
7341593
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Riddle, Robert D
Project Start
2004-01-01
Project End
2009-12-31
Budget Start
2008-01-01
Budget End
2009-12-31
Support Year
5
Fiscal Year
2008
Total Cost
$288,116
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Pharmacology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Hand, Randal; Polleux, Franck (2011) Neurogenin2 regulates the initial axon guidance of cortical pyramidal neurons projecting medially to the corpus callosum. Neural Dev 6:30
Powell, Ashton W; Sassa, Takayuki; Wu, Yongqin et al. (2008) Topography of thalamic projections requires attractive and repulsive functions of Netrin-1 in the ventral telencephalon. PLoS Biol 6:e116
Barnes, Anthony P; Solecki, David; Polleux, Franck (2008) New insights into the molecular mechanisms specifying neuronal polarity in vivo. Curr Opin Neurobiol 18:44-52
Tucker, Eric S; Segall, Samantha; Gopalakrishna, Deepak et al. (2008) Molecular specification and patterning of progenitor cells in the lateral and medial ganglionic eminences. J Neurosci 28:9504-18
Tucker, Eric S; Polleux, Franck; LaMantia, Anthony-Samuel (2006) Position and time specify the migration of a pioneering population of olfactory bulb interneurons. Dev Biol 297:387-401
Hand, Randal; Bortone, Dante; Mattar, Pierre et al. (2005) Phosphorylation of Neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex. Neuron 48:45-62
Polleux, Franck; Lauder, Jean M (2004) Toward a developmental neurobiology of autism. Ment Retard Dev Disabil Res Rev 10:303-17