What is claimed is:
1. A method of converting a stem cell into a ventral neuron which comprises introducing into the stem cell a nucleic acid which expresses homeodomain transcription factor Nkx6.1 protein in the stem cell so as to thereby convert the stem cell into the ventral neuron.
2. The method of claim 1, wherein the nucleic acid introduced into the stem cell incorporates into the chromosomal DNA of the stem cell.
3. The method of claim 1, wherein the nucleic acid is introduced by transfection or transduction.
4. The method of claim 1, wherein the ventral neuron is a motor neuron, a V2 interneuron or a V3 interneuron.
5. A method of diagnosing a motor neuron degenerative disease in a subject which comprises:
a) obtaining a nucleic acid sample from the subject;
b) sequencing the nucleic acid sample; and
c) comparing the nucleic acid sequence of step (b) with a Nkx6.1 nucleic acid sequence from a subject without motor neuron degenerative disease, wherein a difference in the nucleic acid sequence of step (b) from the Nkx6.1 nucleic acid sequence from the subject without motor neuron degenerative disease indicates that the subject has the motor neuron degenerative disease.
6. The method of claim 5, wherein the motor neuron degenerative disease is amyotrophic lateral sclerosis or spinal muscular atrophy.
7. A method of diagnosing a motor neuron degenerative disease in a subject which comprises:
a) obtaining a nucleic acid sample from the subject;
b) performing a restriction digest of the nucleic acid sample with a panel of restriction enzymes;
c) separating the resulting nucleic acid fragments by size fractionation;
d) hybridizing the resulting separated nucleic acid fragments with a nucleic acid probe(s) of at least 15 nucleotide capable of specifically hybridizing with a unique sequence included within the sequence of a nucleic acid molecule encoding a human Nkx6.1 protein, wherein the sequence of the nucleic acid probe is labeled with a detectable marker, and hybridization of the nucleic acid probe(s) with the separated nucleic acid fragments results in labeled probe-fragment bands;
d) detecting labeled probe-fragment bands, wherein the labeled probe-fragment bands have a band pattern specific to the nucleic acid of the subject; and
f) comparing the band pattern of the detected labeled probe-fragment bands of step (d) with a previously determined control sample, wherein the control sample has a unique band pattern specific to the nucleic acid of a subject having the motor neuron degenerative disease, wherein identity of the band pattern of the detected labeled probe-fragment bands of step (d) to the control sample indicates that the subject has the motor neuron degenerative disease.
8. The method of claim 7, wherein the nucleic acid is DNA.
9. The method of claim 7, wherein the nucleic acid is RNA.
10. The method of claim 7, wherein the size fractionation in step (c) is effected by a polyacrylamide or agarose gel.
11. The method of claim 7, wherein the detectable marker is radioactive isotope, enzyme, dye, biotin, a fluorescent label or a chemiluminescent label.
12. The method of claim 7, wherein the motor neuron degenerative disease is amyotrophic lateral sclerosis or spinal muscular atrophy.
13. A method of converting a stem cell into a ventral neuron which comprises introducing into the stem cell a nucleic acid which expresses homeodomain transcription factor Nkx6.2 protein in the stem cell so as to thereby convert the stem cell into the ventral neuron.
14. The method of claim 13, wherein the nucleic acid introduced into the stem cell incorporates into the chromosomal DNA of the stem cell.
15. The method of claim 13, wherein the nucleic acid is introduced by transfection or transduction.
16. The method of claim 13, wherein the ventral neuron is a motor neuron.
17. A method of converting a stem cell into a ventral neuron which comprises introducing into the stem cell a polypeptide which expresses homeodomain transcription factor Nkx6.1 in the stem cell so as to thereby convert the stem cell into the ventral neuron.
18. The method of claim 17, wherein the ventral neuron is a motor neuron, a V2 interneuron or a V3 interneuron.
19. A method of converting a stem cell into a ventral neuron which comprises introducing into the stem cell a polypeptide which expresses homeodomain transcription factor Nkx6.2 in the stem cell so as to thereby convert the stem cell into the ventral neuron.
20. The method of claim 19, wherein the ventral neuron is a motor neuron.
21. A method of diagnosing a neurodegenerative disease in a subject which comprises:
a) obtaining a suitable sample from the subject;
b) extracting nucleic acid from the suitable sample;
c) contacting the resulting nucleic acid with a nucleic acid probe, which nucleic acid probe (i) is capable of hybridizing with the nucleic acid of Nkx6.1 or Nkx6.2 and (ii) is labeled with a detectable marker;
d) removing unbound labeled nucleic acid probe; and
e) detecting the presence of labeled nucleic acid, wherein the presence of labeled nucleic acid indicates that the subject is afflicted with a chronic neurodegenerative disease, thereby diagnosing a chronic neurodegenerative disease in the subject.
22. The method of claim 21, wherein the suitable sample is spinal fluid.
23. The method of claim 21, wherein the nucleic acid is DNA.
24. The method of claim 21, wherein the nucleic acid is RNA.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A self-expiring badge or label comprising:
an upper substrate having an upper surface and a lower surface,
an adhesive activator layer on the lower surface,
a protective layer having a first surface and a second surface, the first surface removably attached to and overlaying the adhesive layer,
a migrating ink pattern on the second surface of the protective layer,
whereby removing the upper substrate and at least a portion of the protective layer leaves a remaining portion having the migrating ink pattern thereon, and contacting the migrating ink pattern to the exposed adhesive activator layer on the lower surface of the upper substrate to activate the migrating ink pattern to migrate through the adhesive activator layer and upper substrate in a selected time interval for viewing from the upper surface of the upper substrate layer to indicate an expired badge or label.
2. The self-expiring badge or label of claim 1, wherein the migrating ink pattern is contacted to a portion of the exposed adhesive activator layer, the remaining portion of the exposed adhesive activator layer for adhesively mounting the badge or label to a surface.
3. The self-expiring badge or label of claim 1, wherein the remaining portion of the protective layer having the migrating ink pattern thereon is folded to contact the migrating ink pattern to the exposed adhesive activator label.
4. The self-expiring badge or label of claim 1, wherein the remaining portion of the protective layer having the migrating ink pattern thereon is folded to contact the migrating ink pattern to a portion of the exposed adhesive activator layer, the remaining portion of the exposed adhesive activator layer for adhesively mounting the badge or label to a surface.