Abstract: The present invention relates to culture systems comprising differentiated stem cells, that may be used for identifying agents useful in treating degenerative nervous system disorders and are suitable for high-throughput screening applications. It is based, at least in part, on the discovery that co-cultures of (i) astrocytes expressing a mutated SODI gene and (ii) stem-cell derived motor neurons manifested cell death via a Bax-dependent mechanism, and modeled motor neuron death in amyotrophic lateral sclerosis.

Abstract: Disclosed are methods for generating a neuron expressing Hoxc8 transcription factor or a caudal motor neuron comprising culturing an embryonic stem cell in a composition which is essentially free of retinoids and comprises an isotonic salt solution, so as to generate the neuron which expresses Hoxc8 transcription factor or the caudal motor neuron. Disclosed are also methods for generating a caudal brachial motor neuron, a thoracic motor neuron, or a lumbar motor neuron from an embryonic stem cell in a composition essentially free of retinoids and comprising ADFNK medium, an amount of FGF-2, or Gdf11 respectively. Disclosed are also methods of transplanting a motor neuron into a subject comprising generating the motor neuron and transplanting the motor neuron into the subject. Disclosed is also a population of motor neuron cells enriched for motor neuron cells expressing Foxp1 and expressing a gene associated with Spinal Muscular Atrophy (SMA) or Amyotrophic Lateral Sclerosis (ALS).

Abstract: The present invention relates to culture systems comprising differentiated stem cells, that may be used for identifying agents useful in treating degenerative nervous system disorders and are suitable for high-throughput screening applications. It is based, at least in part, on the discovery that co-cultures of (i) astrocytes expressing a mutated SODI gene and (ii) stem-cell derived motor neurons manifested cell death via a Bax-dependent mechanism, and modeled motor neuron death in amyotrophic lateral sclerosis.

Abstract: Disclosed are methods for generating a neuron expressing Hoxc8 transcription factor or a caudal motor neuron comprising culturing an embryonic stem cell in a composition which is essentially free of retinoids and comprises an isotonic salt solution, so as to generate the neuron which expresses Hoxc8 transcription factor or the caudal motor neuron. Disclosed are also methods for generating a caudal brachial motor neuron, a thoracic motor neuron, or a lumbar motor neuron from an embryonic stem cell in a composition essentially free of retinoids and comprising ADFNK medium, an amount of FGF-2, or Gdf11 respectively. Disclosed are also methods of transplanting a motor neuron into a subject comprising generating the motor neuron and transplanting the motor neuron into the subject. Disclosed is also a population of motor neuron cells enriched for motor neuron cells expressing Foxp1 and expressing a gene associated with Spinal Muscular Atrophy (SMA) or Amyotrophic Lateral Sclerosis (ALS).

Abstract: This invention provides 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. Provided are methods of diagnosing a motor neuron degenerative disease in a subject. Also provides is a method of treating neuronal degeneration in a subject which comprises implanting in diseased neural tissue of the subject a neural stem cell which comprises an isolated nucleic acid molecule which is capable of expressing homeodomain Nkx6.1 protein under conditions such that the stem cell is converted into a motor neuron after implantation, thereby treating neuronal degeneration in the subject.

Abstract: This invention provides 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 or Nkx6.2 protein in the stem cell so as to thereby convert the stem cell into the ventral neuron. Provided are methods of diagnosing a motor neuron degenerative disease in a subject. Also provides is a method of treating neuronal degeneration in a subject which comprises implanting in diseased neural tissue of the subject a neural stem cell which is capable of expressing homeodomain Nkx6.1 or Nkx6.2 protein under conditions such that the stem cell is converted into a motor neuron after implantation, thereby treating neuronal degeneration in the subject.

Abstract: This invention provides isolated nucleic acids encoding a motor neuron restricted MNR2 protein, and a homeobox HB9 protein. Also provided are purified MNR2 and HB9 proteins, antibodies recognizing these proteins, transgenic animals expressing these proteins, and functionally equivalent analogs of these proteins. Finally, methods are disclosed for inducing differentiation of somatic motor neurons, and for treating diseases related to the lack of normally functioning motor neurons, neurodegenerative diseases, acute nervous system injury, and neuromuscular disease.

Abstract: This invention provides an isolated nucleic acid molecule encoding a motor neuron restricted pattern, MNR2, protein. This invention provides an isolated nucleic acid molecule of at least 15 contiguous nucleotides capable of specifically hybridizing with a unique sequence included within the sequence of the nucleic acid molecule encoding a MNR2 protein. This invention provides a purified MNR2 protein, a polyclonal and monoclonal antibody directed to an epitope of an MNR2 protein. This invention provides a method of inducing differentiation somatic motor neurons which comprises expressing MNR2 protein in any neural progenitor cells. This invention provides a transgenic animal which expresses an MNR2 protein. This invention provides a pharmaceutical composition comprising a MNR2 protein and pharmaceutically acceptable carrier.

Abstract: Provided are genetically engineered cells comprising a neural stem cell and retroviral expression system in the neural stem cell, which is capable of expressing homeodomain transcription factor Nkx6.1 protein but does not express homeodomain transcription factor Irx3 protein or homeodomain transcription factor Nkx2.2 protein; which is capable of expressing homeodomain transcription factor Nkx6.1 protein and homeodomain transcription factor Irx3 protein; and which is capable of expressing homeodomain transcription factor Nkx2.2 protein or homeodomain transcription factor Nkx2.9 protein. Also provided are methods of generating such genetically engineered motor neurons, V2 neurons, and V3 neurons.

Abstract: This invention provides an isolated vertebrate nucleic acid molecule which encodes dorsalin-1. This invention also provides a nucleic acid probe capable of specifically hybridizing with a sequence included within the sequence of a nucleic acid molecule encoding a dorsalin-1. The invention also provides a vector and host vector system for the production of a polypeptide having the biological activity of dorsalin-1 which comprises the above-described vector in a suitable host. This invention also provides a purified vertebrate dorsalin-1. This invention provides a method for stimulating neural crest cell differentiation, a method for regenerating nerve cells, a method for promoting bone growth, a method for promoting wound healing and a method for treating neural tumor using purified dorsalin-1. This invention further provides a pharmaceutical composition comprising purified dorsalin-1 and a pharmaceutically acceptable carrier. Finally, this invention provides an antibody capable of binding to dorsalin-1.

Abstract: This invention provides 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 or Nkx6.2 protein in the stem cell so as to thereby convert the stem cell into the ventral neuron. Provided are methods of diagnosing a motor neuron degenerative disease in a subject. Also provides is a method of treating neuronal degeneration in a subjet which comprises implanting in diseased neural tissue of the subject a neural stem cell which is capable of expressing homeodomain Nkx6.1 or Nkx6.2 protein under conditions such that the stem cell is converted into a motor neuron after implantation, thereby treating neuronal degeneration in the subject.

Abstract: The present invention provides a method for inducing differentiation of an embryonic stem cell into a differentiated neural cell. The present invention further provides a method for producing differentiated neural cells, and a population of cells comprising the differentiated neural cells. Additionally, the present invention provides a method for repopulating a spinal cord in a subject, and a method for treating nervous tissue degeneration in a subject in need of treatment. The present invention further provides neural progenitor cells, differentiated neural cells, and uses of same. Also provided is a transgenic non-human animal containing the differentiated neural cells. The present invention is further directed to a method for isolating a population of differentiated neural cells. Finally, the present invention provides a method for identifying an agent for use in treating a condition associated with neuron degeneration.

Abstract: This invention provides an isolated nucleic acid molecule encoding a vhh-1 protein, an isolated protein which is a vhh-1 protein, vectors comprising an isolated nucleic acid molecule encoding a vhh-1 protein, mammalian cells comprising such vectors, antibodies directed to a vhh-1 protein, nucleic acid probes useful for detecting a nucleic acid molecule encoding a vhh-1 protein, pharmaceutical compositions related to the vhh-1 proteins, nonhuman transgenic animals which express a normal or a mutant vhh-1 protein. This invention further provides methods for inducing differentiation of floor plate cell, motor neuron, generating ventral neurons and treatments for alleviating abnormalities associated with the vhh-1 protein.

Abstract: This invention provides isolated nucleic acids encoding a motor neuron restricted MNR2 protein, and a homeobox HB9 protein. Also provided are purified MNR2 and HB9 proteins, antibodies recognizing these proteins, transgenic animals expressing these proteins, and functionally equivalent analogs of these proteins. Finally, methods are disclosed for inducing differentiation of somatic motor neurons, and for treating diseases related to the lack of normally functioning motor neurons, neurodegenerative diseases, acute nervous system injury, and neuromuscular disease.

Abstract: This invention provides an isolated nucleic acid molecule encoding a vhh-1 protein, an isolated protein which is a vhh-1 protein, vectors comprising an isolated nucleic acid molecule encoding a vhh-1 protein, mamunalian cells comprising such vectors, antibodies directed to a vhh-1 protein, nucleic acid probes useful for detecting a nucleic acid molecule encoding a vhh-1 protein, pharmaceutical compositions related to the vhh-1 proteins, nonhuman transgenic animals which express a normal or a mutant vhh-1 protein. This invention further provides methods for inducing differentiation of floor plate cell, motor neuron, generating ventral neurons and treatments for alleviating abnormalities associated with the vhh-1 protein.

Abstract: This invention provides an isolated nucleic acid molecule encoding a motor neuron restricted pattern, MNR2, protein. This invention provides an isolated nucleic acid molecule of at least 15 contiguous nucleotides capable of specifically hybridizing with a unique sequence included within the sequence of the nucleic acid molecule encoding a MNR2 protein. This invention provides a purified MNR2 protein, a polyclonal and monoclonal antibody directed to an epitope of an MNR2 protein. This invention provides a method of inducing differentiation somatic motor neurons which comprises expressing MNR2 protein in any neural progenitor cells. This invention provides a transgenic animal which expresses an MNR2 protein. This invention provides a pharmaceutical composition comprising a MNR2 protein and pharmaceutically acceptable carrier.

Abstract: This invention provides an isolated vertebrate nucleic acid molecule which encodes dorsalin-1. This invention also provides a nucleic acid probe capable of specifically hybridizing with a sequence included within the sequence of a nucleic acid molecule encoding a dorsalin-1. The invention also provides a vector and host vector system for the production of a polypeptide having the biological activity of dorsalin-1 which comprises the above-described vector in a suitable host. This invention also provides a purified vertebrate dorsalin-1. This invention provides a method for stimulating neural crest cell differentiation, a method for regenerating nerve cells, a method for promoting bone growth, a method for promoting wound healing and a method for treating neural tumor using purified dorsalin-1. This invention further provides a pharmaceutical composition comprising purified dorsalin-1 and a pharmaceutically acceptable carrier. Finally, this invention provides an antibody capable of binding to dorsalin-1.

Abstract: This invention provides an isolated nucleic acid molecule encoding a motor neuron restricted pattern, MNR2, protein. This invention provides an isolated nucleic acid molecule of at least 15 contiguous nucleotides capable of specifically hybridizing with a unique sequence included within the sequence of the nucleic acid molecule encoding a MNR2 protein. This invention provides a purified MNR2 protein, a polyclonal and monoclonal antibody directed to an epitope of an MNR2 protein. This invention provides a method of inducing differentiation somatic motor neurons which comprises expressing MNR2 protein in any neural progenitor cells. This invention provides a transgenic animal which expresses an MNR2 protein. This invention provides a pharmaceutical composition comprising a MNR2 protein and pharmaceutically acceptable carrier.

Abstract: This invention provides a composition comprising an amount of a purified protein selected from a group consisting of bone morphogenetic protein 4, bone morphogenetic protein, bone morphogenetic protein 7, dorsalin-1 and combinations thereof effective to stimulate neural crest cell differentiation and an acceptable carrier. This invention provides different uses of this composition.

Abstract: This invention provides an isolated vertebrate nucleic acid molecule which encodes dorsalin-1. This invention also provides a nucleic acid probe capable of specifically hybridizing with a sequence included within the sequence of a nucleic acid molecule encoding a dorsalin-1. The invention also provides a vector and host vector system for the production of a polypeptide having the biological activity of dorsalin-1 which comprises the above-described vector in a suitable host. This invention also provides a purified vertebrate dorsalin-1. This invention provides a method for stimulating neural crest cell differentiation, a method for regenerating nerve cells, a method for promoting bone growth, a method for promoting wound healing and a method for treating neural tumor using purified dorsalin-1. This invention further provides a pharmaceutical composition comprising purified dorsalin-1 and a pharmaceutically acceptable carrier. Finally, this invention provides an antibody capable of binding to dorsalin-1.