DOPAMINERGIC NEURON PROLIFERATIVE PROGENITOR CELL MARKER Nato3

Abstract

The present invention is a probe, a primer, and an antibody, for detecting a dopaminergic neuron proliferative progenitor cell. According to the present invention, there is provided a polynucleotide probe and a polynucleotide primer for use in the detection or selection of a dopaminergic neuron proliferative progenitor cell, which can hybridize with a polynucleotide consisting of a nucleotide sequence of a Nato3 gene, or a complementary sequence thereto, and an antibody against a Nato3 protein, or a part thereof for use in the detection or selection of a dopaminergic neuron proliferative progenitor cell.

1 - 7 . (canceled) 
     
     
         8 . A method for detecting or selecting a dopaminergic neuron proliferative progenitor cell in a cell sample to be tested, comprising the step of detecting expression of a Nato3 gene in the cell sample to be tested. 
     
     
         9 . The method according to  claim 8 , wherein the step of detecting expression of the Nato3 gene comprises the steps of:
 (a) contacting a polynucleotide derived from the cell sample to be tested, with the polynucleotide probe according to claim  1 ; and   (b) detecting a hybridization complex.   
     
     
         10 . The method according to  claim 9 , wherein in step (a), mRNA prepared from the cell sample to be tested or a complementary DNA (cDNA) transcribed from the mRNA is contacted with the polynucleotide probe. 
     
     
         11 . The method according to  claim 8 , wherein the step of detecting expression of the Nato3 gene comprises the steps of:
 (c) performing a nucleic acid amplification method by using a polynucleotide derived from the cell sample to be tested as a template and the polynucleotide primer according to claim  1 , or the polynucleotide primer set according to claim  5 ; and   (d) detecting a formed amplification product.   
     
     
         12 . The method according to  claim 11 , wherein in step (c), mRNA prepared from the cell sample to be tested or a complementary DNA (cDNA) transcribed from the mRNA is used as a template. 
     
     
         13 . The method according to  claim 8 , wherein the step of detecting expression of the Nato3 gene comprises the steps of
 (e) contacting a protein derived from the cell sample to be tested, with the antibody according to claim  6  or  7 ; and   (f) detecting an antigen-antibody complex.   
     
     
         14 . The method according to  claim 8 , wherein the cell sample to be tested is an ES cell induced to differentiate into a dopaminergic neuron proliferative progenitor cell. 
     
     
         15 . The method according to  claim 14 , wherein the differentiation induction is carried out by an SDIA method. 
     
     
         16 . The method according to  claim 8 , wherein the cell sample to be tested is a cell obtained from a ventral region of an embryo midbrain. 
     
     
         17 . The method according to  claim 8 , wherein a cell in which expression of a dopaminergic neuron proliferative progenitor cell marker gene for other than the Nato3 gene is detected is used as the cell sample to be tested. 
     
     
         18 . The method according to  claim 8 , which further comprises the step of detecting expression of a dopaminergic neuron proliferative progenitor cell marker gene other than the Nato3 gene, after the step of detecting expression of a Nato3 gene in the cell sample to be tested. 
     
     
         19 . The method according to  claim 17  or  18 , wherein the dopaminergic neuron proliferative progenitor cell marker gene other than the Nato3 gene is at least one gene selected from the group consisting of an Lrp4 gene, an Msx1 gene, an Msx2 gene, and a Mash1 gene. 
     
     
         20 - 23 . (canceled) 
     
     
         24 . A kit for detecting or selecting a dopaminergic neuron proliferative progenitor cell, comprising at least the antibody according to claim  6  or  7 . 
     
     
         25 . The kit according to  claim 24 , which further comprises a probe, a primer, a primer set, or an antibody, which can detect the expression of the dopaminergic neuron proliferative progenitor cell marker gene other than the Nato3 gene. 
     
     
         26 . A method for screening for an effective substance for inducing differentiation into a dopaminergic neuron proliferative progenitor cell, comprising the steps of:
 (i) contacting a cell that can differentiate into a dopaminergic neuron proliferative progenitor cell, with a substance to be tested; and   (ii) detecting expression of a Nato3 gene in the cell contacted with the substance to be tested.   
     
     
         27 . The method according to  claim 26 , which further comprises the step of:
 (iii) detecting expression of the dopaminergic neuron proliferative progenitor cell marker gene other than the Nato3 gene, in the cell contacted with the substance to be tested.   
     
     
         28 . The method according to  claim 27 , wherein the dopaminergic neuron proliferative progenitor cell marker gene other than the Nato3 gene is at least one gene selected from the group consisting of an Lrp4 gene, an Msx1 gene, an Msx2 gene, and a Mash1 gene. 
     
     
         29 . A method for producing a dopaminergic neuron proliferative progenitor cell, comprising the steps of:
 (iv) obtaining cells that can contain a dopaminergic neuron proliferative progenitor cell;   (v) detecting or selecting the dopaminergic neuron proliferative progenitor cell, by using the method according to  claim 8 ; and   (vi) culturing the cell detected or selected in step (v).   
     
     
         30 - 35 . (canceled)