Abdominal-B and caudal inhibit the formation of specific neuroblasts in the Drosophila tail region

The central nervous system of Drosophila melanogaster consists of fused segmental units (neuromeres), each generated by a characteristic number of neural stem cells (neuroblasts). In the embryo, thoracic and anterior abdominal neuromeres are almost equally sized and formed by repetitive sets of neuroblasts, whereas the terminal abdominal neuromeres are generated by significantly smaller populations of progenitor cells. Here we investigated the role of the Hox gene Abdominal-B in shaping the terminal neuromeres. We show that the regulatory isoform of Abdominal-B (Abd-B.r) not only confers abdominal fate to specific neuroblasts (e.g. NB6-4) and regulates programmed cell death of several progeny cells within certain neuroblast lineages (e.g. NB3-3) in parasegment 14, but also inhibits the formation of a specific set of neuroblasts in parasegment 15 (including NB7-3). We further show that Abd-B.r requires cooperation of the ParaHox gene caudal to unfold its full competence concerning neuroblast inhibition and specification. Thus, our findings demonstrate that combined action of Abdominal-B and caudal contributes to the size and composition of the terminal neuromeres by regulating both the number and lineages of specific neuroblasts.

[1]  Álvaro E. Bustos,et al.  Predetermined embryonic glial cells form the distinct glial sheaths of the Drosophila peripheral nervous system , 2013, Development.

[2]  D. Perea,et al.  Bithorax-complex genes sculpt the pattern of leucokinergic neurons in the Drosophila central nervous system , 2013, Development.

[3]  C. Rickert,et al.  Neuroblast pattern and identity in the Drosophila tail region and role of doublesex in the survival of sex-specific precursors , 2013, Development.

[4]  Y. Graba,et al.  Antagonism Versus Cooperativity with TALE Cofactors at the Base of the Functional Diversification of Hox Protein Function , 2013, PLoS genetics.

[5]  R. Maeda,et al.  abd-A Regulation by the iab-8 Noncoding RNA , 2012, PLoS genetics.

[6]  Jim Thurmond,et al.  FlyBase 101 – the basics of navigating FlyBase , 2011, Nucleic Acids Res..

[7]  A. Suska,et al.  Segment-specific generation of Drosophila Capability neuropeptide neurons by multi-faceted Hox cues , 2011, Developmental biology.

[8]  S. Thor,et al.  Segment-Specific Neuronal Subtype Specification by the Integration of Anteroposterior and Temporal Cues , 2010, PLoS biology.

[9]  I. Lohmann,et al.  Cellular analysis of newly identified Hox downstream genes in Drosophila. , 2010, European journal of cell biology.

[10]  Eri Hasegawa,et al.  Neuroblast entry into quiescence is regulated intrinsically by the combined action of spatial Hox proteins and temporal identity factors , 2008, Development.

[11]  G. Technau,et al.  Multiple roles for Hox genes in segment-specific shaping of CNS lineages , 2008, Fly.

[12]  G. Technau,et al.  Antagonistic roles for Ultrabithorax and Antennapedia in regulating segment-specific apoptosis of differentiated motoneurons in the Drosophila embryonic central nervous system , 2008, Development.

[13]  Stefan R. Henz,et al.  Comparative analysis of Hox downstream genes in Drosophila , 2007, Development.

[14]  G. Technau,et al.  Generation of cell diversity and segmental pattern in the embryonic central nervous system of Drosophila , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[15]  K. Mechtler,et al.  Asymmetric Segregation of the Tumor Suppressor Brat Regulates Self-Renewal in Drosophila Neural Stem Cells , 2006, Cell.

[16]  M. Gerhard,et al.  The Cdx4 mutation affects axial development and reveals an essential role of Cdx genes in the ontogenesis of the placental labyrinth in mice , 2006, Development.

[17]  Jean L. Chang,et al.  The chordate ParaHox cluster , 2005, Current Biology.

[18]  J. Garcia-Fernández.  Hox, ParaHox, ProtoHox: facts and guesses , 2005, Heredity.

[19]  C. Doe,et al.  Drosophila neuroblast 7‐3 cell lineage: A model system for studying programmed cell death, Notch/Numb signaling, and sequential specification of ganglion mother cell identity , 2005, The Journal of comparative neurology.

[20]  I. Miguel-Aliaga,et al.  Segment-specific prevention of pioneer neuron apoptosis by cell-autonomous, postmitotic Hox gene activity , 2004, Development.

[21]  J. Deutsch.  Segments and parasegments in arthropods: a functional perspective. , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[22]  Janet Rossant,et al.  Cdx2 is essential for axial elongation in mouse development. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  G. Technau,et al.  Molecular markers for identified neuroblasts in the developing brain of Drosophila , 2003, Development.

[24]  F. Hirth,et al.  A Pulse of the Drosophila Hox Protein Abdominal-A Schedules the End of Neural Proliferation via Neuroblast Apoptosis , 2003, Neuron.

[25]  M. Yamaguchi,et al.  The caudal homeodomain protein activates Drosophila E2F gene expression. , 2002, Nucleic acids research.

[26]  W. McGinnis,et al.  The Drosophila Hox Gene Deformed Sculpts Head Morphology via Direct Regulation of the Apoptosis Activator reaper , 2002, Cell.

[27]  S. Forlani,et al.  Cdx1 and Cdx2 have overlapping functions in anteroposterior patterning and posterior axis elongation. , 2002, Development.

[28]  J. Urban,et al.  Hunchback is required for the specification of the early sublineage of neuroblast 7-3 in the Drosophila central nervous system. , 2002, Development.

[29]  H. Reichert,et al.  Differential expression and function of the Drosophila Pax6 genes eyeless and twin of eyeless in embryonic central nervous system development , 2001, Mechanisms of Development.

[30]  J. Skeath.  At the nexus between pattern formation and cell-type specification: the generation of individual neuroblast fates in the Drosophila embryonic central nervous system. , 1999, BioEssays : news and reviews in molecular, cellular and developmental biology.

[31]  C Q Doe,et al.  Clonal analysis of Drosophila embryonic neuroblasts: neural cell types, axon projections and muscle targets. , 1999, Development.

[32]  G. Morata,et al.  Caudal is the Hox gene that specifies the most posterior Drosophile segment , 1999, Nature.

[33]  K. Bhat.  Segment polarity genes in neuroblast formation and identity specification during Drosophila neurogenesis , 1999, BioEssays : news and reviews in molecular, cellular and developmental biology.

[34]  C. Doe,et al.  Neural stem cells: from fly to vertebrates. , 1998, Journal of neurobiology.

[35]  J. Reinitz,et al.  Rapid preparation of a panel of polyclonal antibodies to Drosophila segmentation proteins , 1998, Development Genes and Evolution.

[36]  G. Technau,et al.  Homeotic regulation of segment-specific differences in neuroblast numbers and proliferation in the Drosophila central nervous system , 1998, Mechanisms of Development.

[37]  V. Hartenstein,et al.  The role of morphogenetic cell death during Drosophila embryonic head development. , 1998, Developmental biology.

[38]  N. M. Brooke,et al.  The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster , 1998, Nature.

[39]  C. Doe,et al.  Miranda directs Prospero to a daughter cell during Drosophila asymmetric divisions , 1997, Nature.

[40]  J. Schlossherr,et al.  Automated in situ detection (AISD) of biomolecules , 1997, Development Genes and Evolution.

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

[42]  Y. Jan,et al.  Miranda Is Required for the Asymmetric Localization of Prospero during Mitosis in Drosophila , 1997, Cell.

[43]  G. Technau,et al.  The differentiation of the serotonergic neurons in the Drosophila ventral nerve cord depends on the combined function of the zinc finger proteins Eagle and Huckebein. , 1997, Development.

[44]  K. Chawengsaksophak,et al.  Homeosis and intestinal tumours in Cdx2 mutant mice , 1997, Nature.

[45]  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.

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

[47]  S. Higashijima,et al.  eagle, a member of the steroid receptor gene superfamily, is expressed in a subset of neuroblasts and regulates the fate of their putative progeny in the Drosophila CNS. , 1996, Development.

[48]  P. Gruss,et al.  Disruption of the murine homeobox gene Cdx1 affects axial skeletal identities by altering the mesodermal expression domains of Hox genes , 1995, Cell.

[49]  C. Doe,et al.  New neuroblast markers and the origin of the aCC/pCC neurons in the Drosophila central nervous system , 1995, Mechanisms of Development.

[50]  S. Thor,et al.  The genetics of brain development: Conserved programs in flies and mice , 1995, Neuron.

[51]  F. Beck,et al.  Expression of Cdx‐2 in the mouse embryo and placenta: Possible role in patterning of the extra‐embryonic membranes , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[52]  T. Kornberg,et al.  Analysis of the genes involved in organizing the tail segments of the Drosophila melanogaster embryo , 1995, Mechanisms of Development.

[53]  Kei Ito,et al.  Distribution, classification, and development ofDrosophila glial cells in the late embryonic and early larval ventral nerve cord , 1995, Roux's archives of developmental biology.

[54]  I. Duncan,et al.  Transvection in the iab-5,6,7 region of the bithorax complex of Drosophila: homology independent interactions in trans. , 1995, Genetics.

[55]  G. Morata,et al.  Colinearity and functional hierarchy among genes of the homeotic complexes. , 1994, Trends in genetics : TIG.

[56]  C. Goodman,et al.  Ectopic and increased expression of fasciclin II alters motoneuron growth cone guidance , 1994, Neuron.

[57]  G. Technau,et al.  Early tagma-specific commitment of Drosophila CNS progenitor NB1-1. , 1994, Development.

[58]  G M Rubin,et al.  Expression of baculovirus P35 prevents cell death in Drosophila. , 1994, Development.

[59]  Christian Klämbt,et al.  The Ets transcription factors encoded by the Drosophila gene pointed direct glial cell differentiation in the embryonic CNS , 1994, Cell.

[60]  M. Akam,et al.  Dissecting the temporal requirements for homeotic gene function. , 1994, Development.

[61]  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.

[62]  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.

[63]  H. Steller,et al.  Genetic control of programmed cell death in Drosophila. , 1994, Science.

[64]  C. Wright,et al.  Murine Cdx-4 bears striking similarities to the Drosophila caudal gene in its homeodomain sequence and early expression pattern , 1993, Mechanisms of Development.

[65]  M. Kuziora,et al.  Abdominal-B protein isoforms exhibit distinct cuticular transformations and regulatory activities when ectopically expressed in Drosophila embryos , 1993, Mechanisms of Development.

[66]  N. Patel,et al.  Analysis of the gooseberry locus in Drosophila embryos: gooseberry determines the cuticular pattern and activates gooseberry neuro. , 1993, Development.

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

[68]  Y. Jan,et al.  deadpan, an essential pan-neural gene in Drosophila, encodes a helix-loop-helix protein similar to the hairy gene product. , 1992, Genes & development.

[69]  William McGinnis,et al.  Homeobox genes and axial patterning , 1992, Cell.

[70]  F. Jiménez,et al.  Distribution and function of the lethal of scute gene product during early neurogenesis in Drosophila. , 1991, Development.

[71]  M. Bienz,et al.  Functional dissection of Drosophila Abdominal-B protein , 1991, Mechanisms of Development.

[72]  A. Lloyd,et al.  Molecular definition of the morphogenetic and regulatory functions and the cis-regulatory elements of the Drosophila Abd-B homeotic gene. , 1991, Development.

[73]  E. Sánchez-Herrero.  Control of the expression of the bithorax complex genes abdominal-A and abdominal-B by cis-regulatory regions in Drosophila embryos. , 1991, Development.

[74]  K. Kellerman,et al.  Mutations affecting the stability of the fushi tarazu protein of Drosophila. , 1990, Genes & development.

[75]  F. Karch,et al.  abdA expression in Drosophila embryos. , 1990, Genes & development.

[76]  T. Kornberg,et al.  Region-specific recombination and expression are directed by portions of the Drosophila engrailed promoter. , 1990, Genes & development.

[77]  G. Gibson,et al.  Effects of ectopic expression of caudal during Drosophila development. , 1990, Development.

[78]  M Bienz,et al.  Expression of Abdominal-B homeoproteins in Drosophila embryos. , 1990, Development.

[79]  M. Zavortink,et al.  The morphogenetic and regulatory functions of the Drosophila Abdominal-B gene are encoded in overlapping RNAs transcribed from separate promoters. , 1989, Genes & development.

[80]  E. Lewis,et al.  The molecular genetics of the bithorax complex of Drosophila: characterization of the products of the Abdominal-B domain. , 1989, Genes & development.

[81]  D. Tautz,et al.  A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback , 1989, Chromosoma.

[82]  M. Delorenzi,et al.  Drosophila homoeotic genes encode transcriptional activators similar to mammalian OTF-2 , 1988, Nature.

[83]  D. Weigel,et al.  Terminal versus segmental development in the Drosophila embryo: the role of the homeotic gene fork head , 1988, Roux's archives of developmental biology.

[84]  W. McGinnis,et al.  Different transcripts of the Drosophila Abd‐B gene correlate with distinct genetic sub‐functions. , 1988, The EMBO journal.

[85]  M. Delorenzi,et al.  Evidence that the Abdominal‐B r element function is conferred by a trans‐regulatory homeoprotein. , 1988, The EMBO journal.

[86]  E. Sánchez-Herrero,et al.  The Abdominal‐B gene of Drosophila melanogaster: overlapping transcripts exhibit two different spatial distributions , 1988, The EMBO journal.

[87]  G. Jürgens.  Head and tail development of the Drosophila embryo involves spalt, a novel homeotic gene , 1988, The EMBO journal.

[88]  F. Karch,et al.  The bithorax complex: control of segmental identity. , 1987, Genes & development.

[89]  E. Sánchez-Herrero,et al.  Double and triple mutant combinations of bithorax complex of Drosophila. , 1987, The EMBO journal.

[90]  G. Jürgens.  Segmental organisation of the tail region in the embryo of Drosophila melanogaster , 1987, Roux's archives of developmental biology.

[91]  Marek Mlodzik,et al.  Expression of the caudal gene in the germ line of Drosophila: Formation of an RNA and protein gradient during early embryogenesis , 1987, Cell.

[92]  G. Struhl,et al.  A molecular gradient in early Drosophila embryos and its role in specifying the body pattern , 1986, Nature.

[93]  E. Sánchez-Herrero,et al.  Identification and characterization of a parasegment specific regulatory element of the abdominal-B gene of drosophila , 1986, Cell.

[94]  Robert A. H. White,et al.  Regulation of the Ultrabithorax gene of drosophila by other bithorax complex genes , 1985, Cell.

[95]  E. Lewis,et al.  The abdominal region of the bithorax complex , 1985, Cell.

[96]  W. Gehring,et al.  Isolation of caudal, a Drosophila homeo box‐containing gene with maternal expression, whose transcripts form a concentration gradient at the pre‐blastoderm stage , 1985, The EMBO journal.

[97]  P. O’Farrell,et al.  Development of embryonic pattern in D. melanogaster as revealed by accumulation of the nuclear engrailed protein , 1985, Cell.

[98]  M. Levine,et al.  Spatially regulated expression of homeotic genes in Drosophila. , 1985, Science.

[99]  P. Lawrence,et al.  Parasegments and compartments in the Drosophila embryo , 1985, Nature.

[100]  S. Artavanis-Tsakonas,et al.  opa: A novel family of transcribed repeats shared by the Notch locus and other developmentally regulated loci in D. melanogaster , 1985, Cell.

[101]  E. Sánchez-Herrero,et al.  Genetic organization of Drosophila bithorax complex , 1985, Nature.

[102]  M. Wilcox,et al.  Protein products of the bithorax complex in Drosophila , 1984, Cell.

[103]  J. Weston.  Embryonic development. , 1983, Science.

[104]  E. Lewis.  A gene complex controlling segmentation in Drosophila , 1978, Nature.

[105]  H. Reichert,et al.  Hox genes and brain development in Drosophila. , 2010, Advances in experimental medicine and biology.

[106]  G. Technau,et al.  A critical role for Cyclin E in cell fate determination in the central nervous system of Drosophila melanogaster , 2005, Nature Cell Biology.

[107]  D. Falkenburg,et al.  Drosophila melanogaster , 2005 .

[108]  J. Whittle,et al.  Recessive lethal mutations within the bithorax-complex in Drosophila , 2004, Molecular and General Genetics MGG.

[109]  J. Campos-Ortega,et al.  Fate-mapping in wild-typeDrosophila melanogaster , 2004, Wilhelm Roux's archives of developmental biology.

[110]  V. Hartenstein,et al.  Fate-mapping in wild-typeDrosophila melanogaster , 2004, Wilhelm Roux's archives of developmental biology.

[111]  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.

[112]  M. Kasei.  Distribution, classification, and development of Drosophila glial cells in the late embryonic and early larval ventral nerve cord , 1995 .

[113]  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.

[114]  W. Gehring,et al.  Homeodomain proteins. , 1994, Annual review of biochemistry.

[115]  B I Meyer,et al.  Mouse Cdx-1 expression during gastrulation. , 1993, Development.

[116]  G. Morata.  Homeotic genes of Drosophila. , 1993, Current opinion in genetics & development.

[117]  G. Morata,et al.  Expression and regulation of the abd-A gene of Drosophila. , 1990, Development.

[118]  K. G. Coleman,et al.  Expression of engrailed proteins in arthropods, annelids, and chordates. , 1989, Cell.

[119]  I. Duncan,et al.  The bithorax complex. , 1987, Annual review of genetics.

[120]  V. Hartenstein,et al.  A Fate Map of the Blastoderm , 1985 .

[121]  T. Kaufman,et al.  Cytogenetic Analysis of Chromosome 3 in DROSOPHILA MELANOGASTER: The Homoeotic Gene Complex in Polytene Chromosome Interval 84a-B. , 1980, Genetics.

[122]  R. Khesin,et al.  Molecular Genetics , 1968, Springer Berlin Heidelberg.