Molecular switch regulating neurogenesis
AssigneeThe Salk Institute for Biological Studies
InventorsTomoko Kuwabara, Fred Gage
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Abstract
The present disclosure relates to a novel transcription regulatory master switch involved in neural development. The disclosure provides compositions and methods for regulating neural lineage specific genes and modulating the differentiation of stem cells into neural lineage cells.
Claims24
A method of identifying an agent that regulates differentiation of a stem cell into a neural lineage cell, the method comprising:
- (a) contacting with at least one agent a cell, which cell comprises a polynucleotide that encodes a reporter operably linked to a transcription control sequence, wherein the transcription control sequence comprises one or more LEF/Sox overlapping response elements;
- and,
- (b) detecting a relative change in expression of the reporter, wherein the change in expression is measured in comparison to a control cell, which control cell is not contacted with the agent, thereby identifying the agent that regulates differentiation of the stem cell into a neural lineage cell.
A method of identifying an agent that regulates differentiation of a stem cell into a neural lineage cell, the method comprising:
- contacting a nucleic acid comprising a polynucleotide sequence comprising one or more LEF/Sox overlapping response elements with a reaction mixture comprising
- at least one binding factor capable of specific binding to the LEF/Sox overlapping response element;
- and
- at least one agent;
- and
- detecting a change in binding of a component of the reaction mixture to the nucleic acid, thereby identifying an agent that regulates differentiation of a stem cell into a neural lineage cell.
A method of modulating differentiation of a stem cell into a neural lineage cell, the method comprising expressing in a stem cell at least one polypeptide that binds to a LEF/Sox overlapping response element, wherein binding of the polypeptide induces modulates differentiation of the stem cell into a neural lineage cell.
A recombinant nucleic acid comprising a heterologous polynucleotide sequence operably linked to a transcription control sequence, which transcription control sequence comprises one or more LEF/Sox overlapping response elements.
Dependencies are inferred from the claim text.