Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity.

One of the first steps in neurogenesis is the diversification of cells along the dorsoventral axis. In Drosophila the central nervous system develops from three longitudinal columns of cells: ventral cells that express the vnd/nk2 homeobox gene, intermediate cells, and dorsal cells that express the msh homeobox gene. Here we describe a new Drosophila homeobox gene, intermediate neuroblasts defective (ind), which is expressed specifically in the intermediate column cells. ind is essential for intermediate column development: Null mutants have a transformation of intermediate to dorsal column neuroectoderm fate, and only 10% of the intermediate column neuroblasts develop. The establishment of dorsoventral column identity involves negative regulation: Vnd represses ind in the ventral column, whereas ind represses msh in the intermediate column. Vertebrate genes closely related to vnd (Nkx2.1 and Nkx2.2), ind (Gsh1 and Gsh2), and msh (Msx1 and Msx3) are expressed in corresponding ventral, intermediate, and dorsal domains during vertebrate neurogenesis, raising the possibility that dorsoventral patterning within the central nervous system is evolutionarily conserved.

[1]  B. Shilo,et al.  A thousand and one roles for the Drosophila EGF receptor. , 1997, Trends in genetics : TIG.

[2]  S. Carroll,et al.  Specification of neuroblast identity in the Drosophila embryonic central nervous system by gooseberry-distal , 1995, Nature.

[3]  M. Frasch,et al.  msh may play a conserved role in dorsoventral patterning of the neuroectoderm and mesoderm , 1996, Mechanisms of Development.

[4]  C. Rickert,et al.  The embryonic central nervous system lineages of Drosophila melanogaster. II. Neuroblast lineages derived from the dorsal part of the neuroectoderm. , 1996, Developmental biology.

[5]  P. Holland,et al.  Cloning and evolutionary analysis of msh-like homeobox genes from mouse, zebrafish and ascidian. , 1991, Gene.

[6]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[7]  M. Johnston,et al.  Identifying DNA-Binding Sites and Analyzing DNA-Binding Domains Using a Yeast Selection System , 1993 .

[8]  M. Nirenberg,et al.  Dorsal-ventral patterning genes restrict NK-2 homeobox gene expression to the ventral half of the central nervous system of Drosophila embryos. , 1995, Developmental biology.

[9]  C. Rickert,et al.  The Embryonic Central Nervous System Lineages ofDrosophila melanogaster , 1996 .

[10]  M. Nirenberg,et al.  Interactions of the vnd/NK-2 homeodomain with DNA by nuclear magnetic resonance spectroscopy: basis of binding specificity. , 1997, Biochemistry.

[11]  K. White,et al.  Genetic and developmental analysis of the locus vnd in Drosophila melanogaster. , 1983, Genetics.

[12]  C. Doe,et al.  Biochemical analysis of ++Prospero protein during asymmetric cell division: cortical Prospero is highly phosphorylated relative to nuclear Prospero. , 1998, Developmental biology.

[13]  J. Morris,et al.  Repression of Pax-2 by WT1 during normal kidney development. , 1995, Development.

[14]  C. Doe,et al.  Establishing neuroblast-specific gene expression in the Drosophila CNS: huckebein is activated by Wingless and Hedgehog and repressed by Engrailed and Gooseberry. , 1997, Development.

[15]  Prof. Dr. José A. Campos-Ortega,et al.  The Embryonic Development of Drosophila melanogaster , 1997, Springer Berlin Heidelberg.

[16]  N. Patel,et al.  Imaging neuronal subsets and other cell types in whole-mount Drosophila embryos and larvae using antibody probes. , 1994, Methods in cell biology.

[17]  R. McKay,et al.  Identification of target genes regulated by homeotic proteins in Drosophila melanogaster through genetic selection of Ultrabithorax protein-binding sites in yeast. , 1995, Genetics.

[18]  M. Levine,et al.  Threshold responses to the dorsal regulatory gradient and the subdivision of primary tissue territories in the Drosophila embryo. , 1996, Current opinion in genetics & development.

[19]  R. Bodmer The gene tinman is required for specification of the heart and visceral muscles in Drosophila. , 1993, Development.

[20]  M. Pardue Looking at polytene chromosomes. , 1994, Methods in cell biology.

[21]  N. Perrimon,et al.  The Drosophila spitz gene encodes a putative EGF-like growth factor involved in dorsal-ventral axis formation and neurogenesis. , 1992, Genes & development.

[22]  R. Holmgren,et al.  Ectopic expression of either the Drosophila gooseberry-distal or proximal gene causes alterations of cell fate in the epidermis and central nervous system. , 1994, Development.

[23]  F. Kafatos,et al.  Functional cDNA libraries from Drosophila embryos. , 1988, Journal of molecular biology.

[24]  T. Lufkin,et al.  Msx3: a novel murine homologue of the Drosophila msh homeoɡ gene restricted to the dorsal embryonic central nervous system , 1996, Mechanisms of Development.

[25]  B. Shilo,et al.  Establishment of ventral cell fates in the Drosophila embryonic ectoderm requires DER, the EGF receptor homolog. , 1993, Genes & development.

[26]  K. Saigo,et al.  hedgehog signaling independent of engrailed and wingless required for post-S1 neuroblast formation in Drosophila CNS. , 1996, Development.

[27]  E. L. Ferguson Conservation of dorsal-ventral patterning in arthropods and chordates. , 1996, Current opinion in genetics & development.

[28]  W. Chia,et al.  Klumpfuss, a putative Drosophila zinc finger transcription factor, acts to differentiate between the identities of two secondary precursor cells within one neuroblast lineage. , 1997, Genes & development.

[29]  R. Lehmann,et al.  In situ hybridization to RNA. , 1994, Methods in cell biology.

[30]  A. Nose,et al.  The role of the msh homeobox gene during Drosophila neurogenesis: implication for the dorsoventral specification of the neuroectoderm. , 1997, Development.

[31]  A. Riggs,et al.  Genomic sequencing. , 1993, Methods in molecular biology.

[32]  J. Campos-Ortega Genetic mechanisms of early neurogenesis in Drosophila melanogaster , 1994, Journal of Physiology - Paris.

[33]  E. Bier Anti-Neural-Inhibition: A Conserved Mechanism for Neural Induction , 1997, Cell.

[34]  S. Carroll,et al.  The ventral nervous system defective gene controls proneural gene expression at two distinct steps during neuroblast formation in Drosophila. , 1994, Development.

[35]  T. Dick,et al.  The role of a Drosophila POU homeo domain gene in the specification of neural precursor cell identity in the developing embryonic central nervous system. , 1993, Genes & development.

[36]  K. Bhat The patched signaling pathway mediates repression of gooseberry allowing neuroblast specification by wingless during Drosophila neurogenesis. , 1996, Development.

[37]  C. Doe,et al.  Neuroblast specification and formation regulated by wingless in the Drosophila CNS. , 1993, Science.

[38]  P. Schedl,et al.  Requirement for engrailed and invected genes reveals novel regulatory interactions between engrailed/invected, patched, gooseberry and wingless during Drosophila neurogenesis. , 1997, Development.

[39]  Thomas C. Kaufman,et al.  brahma: A regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2 SWI2 , 1992, Cell.

[40]  S. Wilson,et al.  Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of neuronal differentiation in the embryonic forebrain. , 1995, Development.

[41]  A. Aguzzi,et al.  Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis. , 1992, Genes & development.

[42]  B. Shilo,et al.  Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. , 1995, Genes & development.

[43]  S. Carroll,et al.  Regulation of proneural gene expression and cell fate during neuroblast segregation in the Drosophila embryo. , 1992, Development.

[44]  W. Gilbert,et al.  Sequencing end-labeled DNA with base-specific chemical cleavages. , 1980, Methods in enzymology.

[45]  C. Doe Molecular markers for identified neuroblasts and ganglion mother cells in the Drosophila central nervous system. , 1992, Development.

[46]  C Q Doe,et al.  The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm. , 1996, Developmental biology.

[47]  R J Schwartz,et al.  Identification of Novel DNA Binding Targets and Regulatory Domains of a Murine Tinman Homeodomain Factor, nkx-2.5(*) , 1995, The Journal of Biological Chemistry.

[48]  Gurparkash Singh,et al.  Gsh‐1: A novel murine homeobox gene expressed in the central nervous system , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[49]  C. Doe,et al.  Dorsoventral patterning in the Drosophila central nervous system: the vnd homeobox gene specifies ventral column identity. , 1998, Genes & development.

[50]  C. Doe,et al.  huckebein specifies aspects of CNS precursor identity required for motoneuron axon pathfinding , 1995, Neuron.

[51]  M. Noll,et al.  Cloning of the extra sex combs gene of Drosophila and its identification by P‐element‐mediated gene transfer , 1985, The EMBO journal.

[52]  L. Velasco,et al.  vnd, a gene required for early neurogenesis of Drosophila, encodes a homeodomain protein. , 1995, The EMBO journal.

[53]  S. Easter,et al.  Pax-6 functions in boundary formation and axon guidance in the embryonic mouse forebrain. , 1997, Development.

[54]  M. Frasch,et al.  tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila. , 1993, Genes & development.

[55]  S. Potter,et al.  Altered forebrain and hindbrain development in mice mutant for the Gsh-2 homeobox gene. , 1997, Developmental biology.

[56]  S. Carroll,et al.  The achaete‐scute complex: generation of cellular pattern and fate within the Drosophila nervous system , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.