Neurogenesis inducing gene

Details Neurogenesis inducing gene Neurogenesis inducing gene

1998-09-28

2001-08-21

Hauda, Karen M. (Department: 1632)

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

C435S252300, C435S325000, C435S458000, C435S320100, C536S023500

Reexamination Certificate

active

06277594

ABSTRACT:

This application claims priority benefit to Japanese patent application numbers 86979/1998, filed Mar. 31, 1998, and 121456/1998, filed Apr. 30, 1998.
FIELD OF THE INVENTION
The present invention relates to a neurogenesis inducing gene.
BACKGROUND OF THE INVENTION
The early process of vertebrate neurogenesis is divided into several basic processes, such as differentiation into the neural plate (neural induction) and formation and maturation of the neural network from the ectoderm. This early process includes the appearance of neural precursor cells, pattern formation of the nervous system, and proliferation and differentiation of neural precursor cells. For the understanding of the molecular basis of higher brain functions, it is important to elucidate the universal, underlying principles of these processes in all species.
It is known that the early neurogenesis of
Xenopus laevis
is induced by blockade of BMP4 (Bone Morphogenetic Protein 4) signals by noggin, chordin, etc. secreted by the organizer [Sasai, Y. et al.: Nature, 376:333 (1995)]. BMP4 is a factor which induces the ectoderm into epidermal cells; under a condition where BMP4 is activated, cells differentiate into the epidermis.
On the other hand, as genes involved in the control of neural induction (neurogenesis, neural differentiation) which are called proneural genes, Neurogenin, NeuroD, XASH-3, XATH-3 and the like coding for basic-helix-loop-helix (bHLH) transcription factors are known.
However, it is still unknown what regulates the cascade linking the blockage of BMP4 signals to proneural genes.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a neurogenesis inducing protein; a gene coding for the protein; a recombinant vector comprising the gene; a transformant comprising the vector; an antibody against the protein; and a therapeutic agent for diseases of the nervous system.
As a result of extensive and intensive research toward the solution of the above problem, the present inventors have succeeded in isolating a gene having neurogenesis inducing activity from a Xenopus neurula CDNA library. Thus, the present invention has been achieved.
The present invention relates to the following recombinant protein (a) or (b):
(a) a protein consisting of the amino acid sequence shown in SEQ ID NO: 2
(b) a protein which consists of the amino acid sequence shown in SEQ ID NO: 2 having deletion, substitution or addition of at least one amino acid and which has neurogenesis inducing activity.
Further, the present invention relates to a neurogenesis inducing gene coding for the following protein (a) or (b):
(a) a protein consisting of the amino acid sequence shown in SEQ ID NO: 2
(b) a protein which consists of the amino acid sequence shown in SEQ ID NO: 2 having deletion, substitution or addition of at least one amino acid and which has neurogenesis inducing activity;
or a gene which hybridizes with the above gene under stringent conditions and which codes for a protein having neurogenesis inducing activity.
Further, the present invention relates to a gene consisting of the following DNA (c) or (d):
(c) a DNA consisting of the nucleotide sequence shown in SEQ ID NO: 1
(d) a DNA which hybridizes with the DNA consisting of the nucleotide sequence of (c) under stringent conditions and which codes for a protein having neurogenesis inducing activity.
Further, the present invention relates to a recombinant vector comprising any of the genes described above.
Further, the present invention relates to a transformant comprising the above vector.
Further, the present invention relates to a method for producing a neurogenesis inducing protein, comprising culturing the above transformant and recovering the neurogenesis inducing protein from the resultant culture.
Further, the present invention relates to an antibody against the above protein.
Further, the present invention relates to a therapeutic agent for diseases of the nervous system comprising the above protein as an active ingredient, or an agent for gene therapy for nervous diseases comprising the above gene. As the nervous disease, at least one disease selected from the group consisting of Alzheimer's disease, amyotrophic lateral sclerosis, spinocerebellar degeneration, Parkinson's disease and cerebral ischemia may be given.


REFERENCES:
Verma et al. Nature 389: 239-242, especially p. 239, Sep. 1997.*
Anderson et al. Nature 392: 25-30, especially pp. 25 and 30, Apr. 199.*
Eck and Wilson. In Goodman and Gilmans the Pharmacological basis ofTherapeutics. McGraw-Hill publishers. pp. 77-101, especially 77-82, in particular p. 81 column 2 to p. 82 column 2, 1995.*
Upton et al. Mol Endocrinol 9: 83-92, abstract only, Aug. 1992.*
Frade et al. Development 122: 2497-2506, see especially lines 1-4 of abstract, Aug. 1996.*
Aruga et al. J Neurochem 63: 1880-1890, see especially Fig. 1, p. 1882, 1994.*
Aruga et al. GenEmbl Accession No. D32167, Jul. 1994.*
Aruga et al., “The mouse Zic gene family Homologues of the Drosophila pair-rule gene odd-paired,”J. Biol. Chem. 271: 1043-1047 [1996].
Becker et al., “High-efficiency transformation of yeast by electroporation,”Methods Enzymol., 194:182-187 [1990].
Benedyk et al., “Odd-paired: a zinc finger pair-rule protein required for the timely activation of engrailed and wingless in Drosophila embryos,”Genes Dev., 8:105-117 [1994].
Chitnis et al., “Primary neurogenesis in Xenopus embryos regulated by a homologue of the Drosophila neurogenic gene Delta,”Nature375:761-766 [1995].
Cohen et al., “Nonchromosomal antibiotic resistance in bacteria: genetic transformation ofEscherichia coliby R-Factor DNA,”Proc. Natl. Acad. Sci. USA69:2110-2114 [1972].
Ferreiro et al., “XASH genes promote neurogenesis in Xenopus embryos,”Development120:3649-3655 [1994].
Godsave et al., “Clonal analysis of mesoderm induction inXenopus laevis,” Dev. Biol. 134:486-490 [1989].
Grunz et al., “Neural differentiation ofXenopus laevisectoderm takes place after disaggregation and delayed reaggregation without inducer,”Cell Differ. Dev. 28:211-218 [1989].
Hanahan, “Studies on transformation ofEscherichia coliwith plasmids,”J. Mol. Bio., 166:557-580 [1983].
Harland, “In situ hybridization: an improved whole-mount method for Xenopus embryos,”Methods in Cell Biol., 36:685-694 [1991].
Hemmati-Brivanlou et. al., “Cephalic expression and molecular characterization ofXenopus en-2,” Development111(3):715-724 [1991].
Hemmati-Brivanlou et al., “Follistatin, an antagonist of activin, is expressed in the Spemann Organizer and displays direct neuralizing activity,”Cell77:283-295 [1994].
Hinnen et al., “Transformation of yeast,”Proc. Natl. Acad. Sci. USA75:1929-1933 [1978].
Ito et al., “Transformation of intact yeast cells treated with alkali cations,”J. Bacteriol., 153:163-168 [1983].
Jones and Woodland, “Development of the ectoderm in Xenopus: tissue specification and the role of cell association and division,”Cell44:345-355 [1986].
Kintner and Melton, “Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction,”Development99:311-325 [1987].
Lamb et al., “Neural induction by the secreted polypeptide Noggin,”Science262:713-718 [1993].
Lee et al., “Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein,”Science268:836-844 [1995].
Newport et al., “A major developmental transition in early Xenopus embryos: I. characterization and timing of cellular changes at the midblastula stage,”Cell30:675-686 [1982].
Oschwald et al., “Localization of a nervous system-specific class II &bgr;-tubulin gene inXenopus laevisembryos by whole-mount in situ hybridization,”Int. J. Dev. Biol. 35:399-405 [1991].
Pearson et al., “Improved tools for biological sequence comparison,”Proc. Natl. Acad. Sci. USA85:2444-2448 [1988].
Sambrook et al.,Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Labor

Affiliated with

Also associated with

Rating

Neurogenesis inducing gene does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Neurogenesis inducing gene, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Neurogenesis inducing gene will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2467643