Lrp4/corin dopamine-producing neuron proliferation precursor cell marker

Abstract

In neuron transplantation therapy, in terms of safety, it is preferable to use a cell population consisting only of a desired type of cells, and to use postmitotic neurons in consideration to avoid the risk of tumorigenesis. Moreover, greater therapeutic effects would be expected through the use of earlier progenitor cells in consideration of post-transplantation viability, proper network formation ability, and such. According to the present invention, Lrp4, a gene that is specifically expressed in dopaminergic neuron proliferative progenitor cells prior to cell cycle exit, was identified. The use of Lrp4 expression in cells as an index allows for the isolation. of cells suitable for transplantation therapy of neurodegenerative diseases such as Parkinson's disease in terms of safety, survival rate, and network formation ability.

1 . A dopaminergic neuron proliferative progenitor cell marker polynucleotide probe comprising a sequence selected from the following nucleotide sequences (1) to (5): 
 (1) a nucleotide sequence complementary to a nucleotide sequence of SEQ ID NO: 1 or 2;    (2) a nucleotide sequence complementary to a nucleotide sequence encoding an amino acid sequence of SEQ ID NO: 3 or 4;    (3) a nucleotide sequence complementary to a nucleotide sequence encoding a sequence lacking a transmembrane domain in an amino acid sequence of SEQ ID NO: 3 or 4;    (4) a nucleotide sequence that hybridizes under stringent conditions with a polynucleotide consisting of a nucleotide sequence of SEQ ID NO: 1 or 2; and,    (5) a nucleotide sequence comprising at least 15 contiguous nucleotides selected from sequences of (1) to (4).    
     
     
         2 . (canceled)  
     
     
         3 . A method of selecting a dopaminergic neuron proliferative progenitor cell, wherein the method comprises the step of contacting the polynucleotide of  claim 1  with a cell sample thought to comprise a dopaminergic neuron proliferative progenitor cell.  
     
     
         4 . (canceled)  
     
     
         5 . A method of selecting a postmitotic dopaminergic neuron progenitor cell comprising the steps of: 
 (1) selecting a dopaminergic neuron proliferative progenitor cell using the method of  claim 3;     (2) culturing the proliferative progenitor cell selected in (1); and,    (3) screening the progenitor cell cultured in (2) using a postmitotic dopaminergic neuron marker.    
     
     
         6 . A dopaminergic neuron proliferative progenitor cell selected using the method of claims  3 .  
     
     
         7 . A method of isolating a gene specific to a dopaminergic neuron proliferative progenitor cell and a gene specific to each maturation stage of the progenitor cell differentiating into a dopaminergic neuron, wherein the method comprises the step of detecting and isolating a gene specifically expressed in the proliferative progenitor cell of  claim 6 , or a cell differentiated, induced, or proliferated from the progenitor cell.  
     
     
         8 . A method of screening using maturation as an index, wherein the method comprises the steps of contacting a test substance with the proliferative progenitor cell of  claim 6 , and detecting the differentiation or proliferation of the progenitor cell induced by the contact.  
     
     
         9 . A postmitotic dopaminergic neuron progenitor cell selected using the method of  claim 5.