Antibodies to vertebrate serrate proteins and fragments

A composition comprising an amount of an isolated antibody which binds to a first Serrate protein;

• and a pharmaceutically acceptable carrier, which first Serrate protein (i) binds a Notch protein, and (ii) is encoded by a first nucleic acid that hybridizes under low stringency conditions to a second nucleic acid, which second nucleic acid consists of a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), said low stringency conditions comprising hybridization in a buffer comprising 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml denatured salmon sperm DNA, and 10% (wt/vol) dextran sulfate, for 18-20 hours at 40° C., washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 55° C., and washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 60° C., which antibody does not bind a Drosophila Serrate protein.

A composition comprising an amount of a fragment or derivative of an insolated antibody to a first Serrate protein containing the binding domain of the antibody;

• and a pharmaceutically acceptable carrier, which first Serrate protein (i) binds a Notch protein, and (ii) is encoded by a first nucleic acid that hybridizes under low stringency conditions to a second nucleic acid, which second nucleic acid consists of a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), said low stringency conditions comprising hybridization in a buffer comprising 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml denatured salmon sperm DNA, and 10% (wt/vol) dextran sulfate, for 18-20 hours at 40° C., washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 55° C., and washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 60° C., which antibody does not bind a Drosophila Serrate protein.

An antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) administering a immunogenic amount of a first Serrate protein to a host animal, which first Serrate protein (i) binds a Notch protein, and (ii) is encoded by a first nucleic acid that hybridizes under low stringency conditions to a second nucleic acid, or its complement, which second nucleic acid consists of a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), said low stringency conditions comprising hybridization in a buffer comprising 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml denatured salmon sperm DNA, and 10% (wt/vol) dextran sulfate, for 18-20 hours at 40° C., washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 55° C., and washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0. 1% SDS, for 1.5 hours at 60° C., such that an antibody to said first Serrate protein is produced by said host animal;
• and
• (b) recovering the antibody.

An antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) administering a immunogenic amount of a fragment of a first Serrate protein to a host animal, in which the fragment comprises a domain of the first Serrate protein selected from the group consisting of the extracellular domain, DSL domain, domain amino-terminal to the DSL domain, epidermal growth factor-likerepeat domain, transmembrane domain, and intracellular domain, which first Serrate protein (i) binds a Notch protein, and (ii) comprises an amino acid sequence encoded by a first nucleic acid that hybridizes under low stringency conditions to a second nucleic acid, or its complement, which second nucleic acid consists of a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), said low stringency conditions comprising hybridization in a buffer comprising 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml denatured salmon sperm DNA, and 10% (wt/vol) dextran sulfate, for 18-20 hours at 40° C., washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0. 1% SDS, for 1.5 hours at 55° C., and washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 60° C., such that an antibody to said fragment is produced by said host animal;
• and
• (b) recovering the antibody.

An antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) administering a immunogenic amount of a protein comprising a fragment of a first Serrate protein to a host animal, in which the fragment comprises a domain of the first Serrate protein selected from the group consisting of the extracellular domain, DSL domain, domain amino-terminal to the DSL domain, epidermal growth factor-likerepeat domain, transmembrane domain, and intracellular domain, which first Serrate protein (i) binds a Notch protein, and (ii) comprises an amino acid sequence encoded by a first nucleic acid that hybridizes under low stringency conditions to a second nucleic acid, or its complement, which second nucleic acid consists of a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), said low stringency conditions comprising hybridization in a buffer comprising 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml denatured salmon sperm DNA, and 10% (wt/vol) dextran sulfate, for 18-20 hours at 40° C., washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 55° C., and washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 60° C., such that an antibody to said Serrate fragment is produced by said host animal;
• and
• (b) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) administering a immunogenic amount of a first Serrate protein to a mouse, which first Serrate protein (i) binds a Notch protein, and (ii) is encoded by a first nucleic acid that hybridizes under low stringency conditions to a second nucleic acid, or its complement, which second nucleic acid consists of a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), said low stringency conditions comprising hybridization in a buffer comprising 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml denatured salmon sperm DNA, and 10% (wt/vol) dextran sulfate, for 18-20 hours at 40° C., washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 55° C., and washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 60° C.;
• (b) recovering spleen cells from said mouse;
• (c) fusing the recovered spleen cells with a cell of a mouse myeloma to generate hybridomas;
• (d) screening to select a hybridoma producing antibody to said first Serrate protein;
• and
• (e) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) fusing a spleen cell from a mouse immunized with an immunogenic amount of a first Serrate protein with a cell of a mouse myeloma to generate hybridomas, which first Serrate protein (i) binds a Notch protein, and (ii) is encoded by a first nucleic acid that hybridizes under low stringency conditions to a second nucleic acid, or its complement, which second nucleic acid consists of a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), said low stringency conditions comprising hybridization in a buffer comprising 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml denatured salmon sperm DNA, and 10% (wt/vol) dextran sulfate, for 18-20 hours at 40° C., washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 55° C., and washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0. 1% SDS, for 1.5 hours at 60° C.;
• (b) screening to select a hybridoma producing antibody to said first Serrate protein;
• and
• (c) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced the a method comprising:

• (a) administering a immunogenic amount of a first Serrate protein to a host animal, which first Serrate protein (i) binds a Notch protein, and (ii) is encoded by a first nucleic acid that hybridizes under low stringency conditions to a second nucleic acid, or its complement, which second nucleic acid consists of a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), said low stringency conditions comprising hybridization in a buffer comprising 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml denatured salmon sperm DNA, and 10% (wt/vol) dextran sulfate, for 18-20 hours at 40° C., washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 55° C., and washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0. 1% SDS, for 1.5 hours at 60° C.;
• (b) recovering lymphocytes from said host animal;
• (c) fusing the recovered lymphocytes with a cell of a myeloma, plastocytoma or lymphoblastoid cell line to generate hybridomas;
• (d) screening to select a hybridoma producing antibody to said first Serrate protein;
• and
• (e) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) fusing a lymphocyte from a host animal immunized with an immunogenic amount of a first Serrate protein with a cell of a myeloma, plastocytoma or lymphoblastoid cell line to generate hybridomas, which first Serrate protein (i) binds a Notch protein, and (ii) is encoded by a first nucleic acid that hybridizes under low stringency conditions to a second nucleic acid, or its complement, which second nucleic acid consists of a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), said low stringency conditions comprising hybridization in a buffer comprising 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml denatured salmon sperm DNA, and 10% (wt/vol) dextran sulfate, for 18-20 hours at 40° C., washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 55° C., and washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 60° C.;
• (b) screening to select a hybridoma producing antibody to said first Serrate protein;
• and
• (c) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) administering a immunogenic amount of a first Serrate protein to a host animal, which first Serrate protein (i) binds a Notch protein, and (ii) is encoded by a first nucleic acid that hybridizes under low stringency conditions to a second nucleic acid, or its complement, which second nucleic acid consists of a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), said low stringency conditions comprising hybridization in a buffer comprising 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml denatured salmon sperm DNA, and 10% (wt/vol) dextran sulfate, for 18-20 hours at 40° C., washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 55° C., and washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 60° C.;
• (b) recovering lymphocytes from said host animal;
• (c) immortalizing the recovered lymphocytes with Epstein-Barr virus to generate immortalized cells;
• (d) screening to select an immortalized cell producing antibody to said first Serrate protein;
• and
• (e) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) immortalizing a lymphocyte from a host animal immunized with an immunogenic amount of a first Serrate protein with Epstein-Barr virus to generate immortalized cells, which first Serrate protein (i) binds a Notch protein, and (ii) is encoded by a first nucleic acid that hybridizes under low stringency conditions to a second nucleic acid, or its complement, which second nucleic acid consists of a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), said low stringency conditions comprising hybridization in a buffer comprising 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml denatured salmon sperm DNA, and 10% (wt/vol) dextran sulfate, for 18-20 hours at 40° C., washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 55° C., and washing in a buffer consisting of 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS, for 1.5 hours at 60° C.;
• (b) screening to select an immortalized cell producing antibody to said first Serrate protein;
• and
• (c) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) administering a immunogenic amount of a Serrate protein to a mouse, which Serrate protein is encoded by a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO 15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5);
• (b) recovering spleen cells from said mouse;
• (c) fusing the recovered spleen cells with a cell of a mouse myeloma to generate hybridomas;
• (d) screening to select a hybridoma producing antibody to said Serrate protein;
• and
• (e) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) fusing a spleen cell from a mouse immunized with an immunogenic amount of a Serrate protein with a cell of a mouse myeloma to generate hybridomas, which Serrate protein is encoded by a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5);
• (b) screening to select a hybridoma producing antibody to said Serrate protein;
• and
• (c) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced the a method comprising:

• (a) administering a immunogenic amount of a Serrate protein to a host animal, which Serrate protein is encoded by a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5);
• (b) recovering lymphocytes from said host animal;
• (c) fusing the recovered lymphocytes with a cell of a myeloma, plastocytoma or lymphoblastoid cell line to generate hybridomas;
• (d) screening to select a hybridoma producing antibody to said Serrate protein;
• and
• (e) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) fusing a lymphocyte from a host animal immunized with an immunogenic amount of a Serrate protein with a cell of a myeloma, plastocytoma or lymphoblastoid cell line to generate hybridomas, which Serrate protein is encoded by a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5);
• (b) screening to select a hybridoma producing antibody to said Serrate protein;
• and
• (c) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) administering a immunogenic amount of a Serrate protein to a host animal, which Serrate protein is encoded by a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:17, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5);
• (b) recovering lymphocytes from said host animal;
• (c) immortalizing the recovered lymphocytes with Epstein-Barr virus to generate immortalized cells;
• (d) screening to select an immortalized cell producing antibody to said Serrate protein;
• and
• (e) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) immortalizing a lymphocyte from a host animal immunized with an immunogenic amount of a Serrate protein with Epstein-Barr virus to generate immortalized cells, which Serrate protein is encoded by a nucleotide sequence selected from the group consisting of the mouse Serrate sequence of SEQ ID NO:15, the antisense strand to the mouse Serrate sequence of SEQ ID NO:15, the mouse Serrate sequence of SEQ ID NO:17, the antisense strand to the mouse Serrate sequence of SEQ ID NO:1 7, the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the antisense strand to the chick Serrate sequence depicted in FIGS. 11A-11B (SEQ ID NO:9), the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5), and the antisense strand to the human Serrate sequence depicted in FIGS. 9A-9G (SEQ ID NO:5);
• (b) screening to select an immortalized cell producing antibody to said Serrate protein;
• and
• (c) recovering the antibody.

A monoclonal antibody, which does not bind a Drosophila Serrate protein, produced by a method comprising:

• (a) fusing a spleen cell from a mouse immunized with an immunogenic amount of a Serrate protein with a cell of a mouse myeloma to generate hybridomas, which Serrate protein consists of the amino acid sequence of SEQ ID NO:6, SEQ ID NO:
• 10, SEQ ID NO:16 or SEQ ID NO:18;
• (b) screening to select a hybridoma producing antibody to said Serrate protein;
• and
• (c) recovering the antibody.