During Drosophila ommatidial development, a single cell is selected within the ommatidial cluster... more During Drosophila ommatidial development, a single cell is selected within the ommatidial cluster to become the R7 photoreceptor neuron. The seven-up gene has been shown to play a role in this process by preventing four other photoreceptor precursors, R3/R4/R1/R6, from adopting the R7 cell fate. The seven-up gene encodes a steroid receptor-like molecule that is expressed only in those four cells that require seven-up function in the developing Drosophila ommatidium. We have examined the functional significance of the spatially restricted expression of seven-up by misexpressing seven-up isoforms. As expected from the function that seven-up performs in R3/R4/R1/R6, ubiquitous expression of seven-up causes transformation of the R7 cell to an R1-R6 cell fate. In addition, depending on the timing and spatial pattern of expression, various other phenotypes are produced including the loss of the R7 cell and the formation of extra R7 cells. Ubiquitous expression of seven-up close to the mor...
with phylogenetic tree analyses, allow at present for the Unified Nomenclature for the designatio... more with phylogenetic tree analyses, allow at present for the Unified Nomenclature for the designation of eight subclasses into which all known three-letter code for different species already estababout gene nomenclature conventions can be obtained at the Hulished by the Committee on Standardization in Human man Gene Nomenclature web site ( Cytogenetics [e.g., (GGA) 2 SEMA3A for chicken, (HSA) nomenclature/) and the links therein. SEMA3A for human, (MMU)Sema3A for mouse, (RNO) 3 The appropriate citation for this letter is: (Semaphorin Nomenclature Committee, 1999). Sema3A for rat, (DRE)SEMA3A for zebrafish; (SAM) 4 The committee consists of: C.S. Goodman,* A.L. Kolodkin (Chair), † Sema-1a for grasshopper, (DME)Sema-1a for Drosophila, Y. Luo, ‡ A.W. Pu ¨schel, § and J.A. Raper. (CEL)Sema-1a for C. elegans, etc.). Given the difficulty * Howard Hughes Medical Institute, Department of Molecular and in firmly establishing ortholog relationships among in-Cell Biology,
The semaphorins are the largest family of repulsive axon guidance molecules. Secreted semaphorins... more The semaphorins are the largest family of repulsive axon guidance molecules. Secreted semaphorins bind neuropilin receptors and repel sensory, sympathetic and motor axons. Here we show that CA1, CA3 and dentate gyrus axons from E15-E17 mouse embryo explants are selectively repelled by entorhinal cortex and neocortex. The secreted semaphorins Sema III and Sema IV and their receptors Neuropilin-1 and -2 are expressed in the hippocampal formation during appropriate stages. Sema III and Sema IV strongly repel CA1, CA3 and dentate gyrus axons; entorhinal axons are only repelled by Sema III. An antibody against Neuropilin-1 blocks the repulsive action of Sema III and the entorhinal cortex, but has no effect on Sema IV-induced repulsion. Thus, chemorepulsion plays a role in axon guidance in the hippocampus, secreted semaphorins are likely to be responsible for this action, and the same axons can be repelled by two distinct semaphorins via two different receptors.
The Drosophila seven-up (svp) gene was isolated as a lethal insertion in an "enhancer trap" scree... more The Drosophila seven-up (svp) gene was isolated as a lethal insertion in an "enhancer trap" screen. It is expressed and required in photoreceptor cell precursors RI, R3, R4, and R6 during eye development. The absence of svp+ function causes a transformation of these cells toward an R7 cell fate, as judged by morphology and expression of an RFspecific marker. This transformation depends in part on the sevenless gene product. Our results show that svp is involved in control of cell fate during the generation of neuronal diversity. Molecular analysis of svp reveals that it is a member of the steroid receptor gene superfamily and is likely to be a Drosophila homolog of the human transcription factor COUP
The financial suuoort of the Natural Sciences and Enei neeri ne Research Counci l of Canada, thro... more The financial suuoort of the Natural Sciences and Enei neeri ne Research Counci l of Canada, thro& grants to H.L.A. and a studen&p to g.A.S., is gratefully acknowledged. We thank M. HegstrGm-Wojtowicz for technical help, Dr. L. Marin for hel p with electron microscopy, Mr. A. Shayan for hel p with photography and reconstructions, and Drs. R. Cooper, M. Msghina, and G. Davis for comments on this manuscript. H.L.A. is a member of the Medi cal Research Counci l of Canada Group i n Nerve Cel l s and Svnaoscs.
postsynaptic cell independently and to study the consequences on both the structure and the funct... more postsynaptic cell independently and to study the consequences on both the structure and the function of the synapse in vivo. The Drosophila NMJ shares several important features with central excitatory synapses in the vertebrate
Proceedings of the National Academy of Sciences, 2005
The regulators of the Rho-family GTPases, GTPase-activating proteins (GAPs) and guanine exchange ... more The regulators of the Rho-family GTPases, GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs), play important roles in axon guidance. By means of a functional genomic study of the Rho-family GEFs and GAPs in Drosophila , we have identified a Rho-family GAP, CrossGAP (CrGAP), which is involved in Roundabout (Robo) receptor-mediated repulsive axon guidance. CrGAP physically associates with the Robo receptor. Too much or too little CrGAP activity leads to defects in Robo-mediated repulsion at the midline choice point. The CrGAP gain-of-function phenotype mimics the loss-of-function phenotypes of both Robo and Rac. Dosage-sensitive genetic interactions among CrGAP, Robo, and Rac support a model in which CrGAP transduces signals downstream of Robo receptor to regulate Rac-dependent cytoskeletal changes.
Proceedings of the National Academy of Sciences, 1996
It has long been suspected that proteolytic activity associated with advancing growth cones may b... more It has long been suspected that proteolytic activity associated with advancing growth cones may be required for axon extension. We have isolated mutations in the kuzbanian ( kuz ) gene, which is expressed in the nervous system and encodes a putative zinc metalloprotease with a disintegrin domain. Drosophila embryos with loss-of-function mutations in kuz have dramatic defects in the development of central nervous system axon pathways, with many axons stalling and failing to extend through the nerve cord. This phenotype is rescued by panneural expression of kuz mRNA in the embryo. These results show that the Kuz metalloprotease is required for axon extension, suggesting a requirement for proteolytic activity at the growth cone surface.
L'invention concerne des compositions et des methodes relatives a des constructions comprenan... more L'invention concerne des compositions et des methodes relatives a des constructions comprenant un polypetide SIRP-α, y compris des variants SIRP-α. Les constructions peuvent etre mises au point de diverses manieres pour repondre a des facteurs environnementaux, tels que le pH, l'hypoxie, et/ou la presence d'enzymes associes a une tumeur ou d'antigenes associes a une tumeur. Les constructions selon l'invention peuvent etre utilisees pour traiter diverses maladies, telles que le cancer, de preference, une tumeur solide ou un cancer hematologique.
... BIOLOGY 111, 193205 (1985) Early Events in Insect Neurogenesis Development and Segmental Diff... more ... BIOLOGY 111, 193205 (1985) Early Events in Insect Neurogenesis Development and Segmental Differences in the Pattern of Neuronal Precursor Cells CHRIS Q. DOE AND COREY S. GOODMAN Department of Biological Sciences, Stanford University, Stanford, California ...
During Drosophila ommatidial development, a single cell is selected within the ommatidial cluster... more During Drosophila ommatidial development, a single cell is selected within the ommatidial cluster to become the R7 photoreceptor neuron. The seven-up gene has been shown to play a role in this process by preventing four other photoreceptor precursors, R3/R4/R1/R6, from adopting the R7 cell fate. The seven-up gene encodes a steroid receptor-like molecule that is expressed only in those four cells that require seven-up function in the developing Drosophila ommatidium. We have examined the functional significance of the spatially restricted expression of seven-up by misexpressing seven-up isoforms. As expected from the function that seven-up performs in R3/R4/R1/R6, ubiquitous expression of seven-up causes transformation of the R7 cell to an R1-R6 cell fate. In addition, depending on the timing and spatial pattern of expression, various other phenotypes are produced including the loss of the R7 cell and the formation of extra R7 cells. Ubiquitous expression of seven-up close to the mor...
with phylogenetic tree analyses, allow at present for the Unified Nomenclature for the designatio... more with phylogenetic tree analyses, allow at present for the Unified Nomenclature for the designation of eight subclasses into which all known three-letter code for different species already estababout gene nomenclature conventions can be obtained at the Hulished by the Committee on Standardization in Human man Gene Nomenclature web site ( Cytogenetics [e.g., (GGA) 2 SEMA3A for chicken, (HSA) nomenclature/) and the links therein. SEMA3A for human, (MMU)Sema3A for mouse, (RNO) 3 The appropriate citation for this letter is: (Semaphorin Nomenclature Committee, 1999). Sema3A for rat, (DRE)SEMA3A for zebrafish; (SAM) 4 The committee consists of: C.S. Goodman,* A.L. Kolodkin (Chair), † Sema-1a for grasshopper, (DME)Sema-1a for Drosophila, Y. Luo, ‡ A.W. Pu ¨schel, § and J.A. Raper. (CEL)Sema-1a for C. elegans, etc.). Given the difficulty * Howard Hughes Medical Institute, Department of Molecular and in firmly establishing ortholog relationships among in-Cell Biology,
The semaphorins are the largest family of repulsive axon guidance molecules. Secreted semaphorins... more The semaphorins are the largest family of repulsive axon guidance molecules. Secreted semaphorins bind neuropilin receptors and repel sensory, sympathetic and motor axons. Here we show that CA1, CA3 and dentate gyrus axons from E15-E17 mouse embryo explants are selectively repelled by entorhinal cortex and neocortex. The secreted semaphorins Sema III and Sema IV and their receptors Neuropilin-1 and -2 are expressed in the hippocampal formation during appropriate stages. Sema III and Sema IV strongly repel CA1, CA3 and dentate gyrus axons; entorhinal axons are only repelled by Sema III. An antibody against Neuropilin-1 blocks the repulsive action of Sema III and the entorhinal cortex, but has no effect on Sema IV-induced repulsion. Thus, chemorepulsion plays a role in axon guidance in the hippocampus, secreted semaphorins are likely to be responsible for this action, and the same axons can be repelled by two distinct semaphorins via two different receptors.
The Drosophila seven-up (svp) gene was isolated as a lethal insertion in an "enhancer trap" scree... more The Drosophila seven-up (svp) gene was isolated as a lethal insertion in an "enhancer trap" screen. It is expressed and required in photoreceptor cell precursors RI, R3, R4, and R6 during eye development. The absence of svp+ function causes a transformation of these cells toward an R7 cell fate, as judged by morphology and expression of an RFspecific marker. This transformation depends in part on the sevenless gene product. Our results show that svp is involved in control of cell fate during the generation of neuronal diversity. Molecular analysis of svp reveals that it is a member of the steroid receptor gene superfamily and is likely to be a Drosophila homolog of the human transcription factor COUP
The financial suuoort of the Natural Sciences and Enei neeri ne Research Counci l of Canada, thro... more The financial suuoort of the Natural Sciences and Enei neeri ne Research Counci l of Canada, thro& grants to H.L.A. and a studen&p to g.A.S., is gratefully acknowledged. We thank M. HegstrGm-Wojtowicz for technical help, Dr. L. Marin for hel p with electron microscopy, Mr. A. Shayan for hel p with photography and reconstructions, and Drs. R. Cooper, M. Msghina, and G. Davis for comments on this manuscript. H.L.A. is a member of the Medi cal Research Counci l of Canada Group i n Nerve Cel l s and Svnaoscs.
postsynaptic cell independently and to study the consequences on both the structure and the funct... more postsynaptic cell independently and to study the consequences on both the structure and the function of the synapse in vivo. The Drosophila NMJ shares several important features with central excitatory synapses in the vertebrate
Proceedings of the National Academy of Sciences, 2005
The regulators of the Rho-family GTPases, GTPase-activating proteins (GAPs) and guanine exchange ... more The regulators of the Rho-family GTPases, GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs), play important roles in axon guidance. By means of a functional genomic study of the Rho-family GEFs and GAPs in Drosophila , we have identified a Rho-family GAP, CrossGAP (CrGAP), which is involved in Roundabout (Robo) receptor-mediated repulsive axon guidance. CrGAP physically associates with the Robo receptor. Too much or too little CrGAP activity leads to defects in Robo-mediated repulsion at the midline choice point. The CrGAP gain-of-function phenotype mimics the loss-of-function phenotypes of both Robo and Rac. Dosage-sensitive genetic interactions among CrGAP, Robo, and Rac support a model in which CrGAP transduces signals downstream of Robo receptor to regulate Rac-dependent cytoskeletal changes.
Proceedings of the National Academy of Sciences, 1996
It has long been suspected that proteolytic activity associated with advancing growth cones may b... more It has long been suspected that proteolytic activity associated with advancing growth cones may be required for axon extension. We have isolated mutations in the kuzbanian ( kuz ) gene, which is expressed in the nervous system and encodes a putative zinc metalloprotease with a disintegrin domain. Drosophila embryos with loss-of-function mutations in kuz have dramatic defects in the development of central nervous system axon pathways, with many axons stalling and failing to extend through the nerve cord. This phenotype is rescued by panneural expression of kuz mRNA in the embryo. These results show that the Kuz metalloprotease is required for axon extension, suggesting a requirement for proteolytic activity at the growth cone surface.
L'invention concerne des compositions et des methodes relatives a des constructions comprenan... more L'invention concerne des compositions et des methodes relatives a des constructions comprenant un polypetide SIRP-α, y compris des variants SIRP-α. Les constructions peuvent etre mises au point de diverses manieres pour repondre a des facteurs environnementaux, tels que le pH, l'hypoxie, et/ou la presence d'enzymes associes a une tumeur ou d'antigenes associes a une tumeur. Les constructions selon l'invention peuvent etre utilisees pour traiter diverses maladies, telles que le cancer, de preference, une tumeur solide ou un cancer hematologique.
... BIOLOGY 111, 193205 (1985) Early Events in Insect Neurogenesis Development and Segmental Diff... more ... BIOLOGY 111, 193205 (1985) Early Events in Insect Neurogenesis Development and Segmental Differences in the Pattern of Neuronal Precursor Cells CHRIS Q. DOE AND COREY S. GOODMAN Department of Biological Sciences, Stanford University, Stanford, California ...
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