Abstract

This grant is aimed at studying the roles of three mouse Nkx homeodomain transcription factors, Nkx2.1, 2.2 and 6.1, in development of the basal plate of the CNS. The genes are expressed in distinct and overlapping expression patterns in the basal plate at different anterior-posterior positions. Work of Rubenstein and others have shown that all three genes are required for aspects of ventral CNS development. Dr. Rubentsein proposes to further study these three genes by carrying out a similar set of experiments for each gene. He will characterize null mutants by marker gene analysis to determine whether specification of certain cell types is altered and analyze cell proliferation, cell death and cell migration in the affected regions. He will complement these studies with gain- of-function studies by ectopically expressing the genes in early chick brain to determine whether they are sufficient to induce ventral cell types. He will also study double mutants to address overlapping gene functions and analyze in more detail expression patterns of these genes later in development and in the adult. A collaborator, Dr. Puelles, will visit the lab twice, for two months each, to help analyze the expression patterns and morphological mutant phenotypes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA012462-04
Application #
6515685
Study Section
Special Emphasis Panel (ZRG1-MDCN-6 (01))
Program Officer
Wu, Da-Yu
Project Start
1999-05-01
Project End
2004-02-29
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
4
Fiscal Year
2002
Total Cost
$226,249
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Pan, Qiuping; Li, Changgong; Xiao, Jing et al. (2004) In vivo characterization of the Nkx2.1 promoter/enhancer elements in transgenic mice. Gene 331:73-82
Flames, Nuria; Long, Jason E; Garratt, Alistair N et al. (2004) Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1. Neuron 44:251-61
Yun, Kyuson; Garel, Sonia; Fischman, Seth et al. (2003) Patterning of the lateral ganglionic eminence by the Gsh1 and Gsh2 homeobox genes regulates striatal and olfactory bulb histogenesis and the growth of axons through the basal ganglia. J Comp Neurol 461:151-65
Marin, Oscar; Rubenstein, John L R (2003) Cell migration in the forebrain. Annu Rev Neurosci 26:441-83
Zhao, Yangu; Marin, Oscar; Hermesz, Edit et al. (2003) The LIM-homeobox gene Lhx8 is required for the development of many cholinergic neurons in the mouse forebrain. Proc Natl Acad Sci U S A 100:9005-10
Marin, Oscar; Plump, Andrew S; Flames, Nuria et al. (2003) Directional guidance of interneuron migration to the cerebral cortex relies on subcortical Slit1/2-independent repulsion and cortical attraction. Development 130:1889-901
Anderson, Stewart A; Kaznowski, Christine E; Horn, Carrie et al. (2002) Distinct origins of neocortical projection neurons and interneurons in vivo. Cereb Cortex 12:702-9
Bagri, Anil; Marin, Oscar; Plump, Andrew S et al. (2002) Slit proteins prevent midline crossing and determine the dorsoventral position of major axonal pathways in the mammalian forebrain. Neuron 33:233-48
Marin, Oscar; Baker, Joshua; Puelles, Luis et al. (2002) Patterning of the basal telencephalon and hypothalamus is essential for guidance of cortical projections. Development 129:761-73
Anderson, S A; Marin, O; Horn, C et al. (2001) Distinct cortical migrations from the medial and lateral ganglionic eminences. Development 128:353-63

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