Functional equivalence of Hox gene products in the specification of the tritocerebrum during embryonic brain development of Drosophila

Development ◽  
2001 ◽  
Vol 128 (23) ◽  
pp. 4781-4788 ◽  
Author(s):  
Frank Hirth ◽  
Thomas Loop ◽  
Boris Egger ◽  
David F. B. Miller ◽  
Thomas C. Kaufman ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Gene Action ◽  
Regulatory Elements ◽  
Functional Equivalence ◽  
Embryonic Brain ◽  
Gene Products ◽  
Hox Proteins ◽  
Hox Gene ◽  
Neuronal Identity ◽  
Embryonic Brain Development

Hox genes encode evolutionarily conserved transcription factors involved in the specification of segmental identity during embryonic development. This specification of identity is thought to be directed by differential Hox gene action, based on differential spatiotemporal expression patterns, protein sequence differences, interactions with co-factors and regulation of specific downstream genes. During embryonic development of the Drosophila brain, the Hox gene labial is required for the regionalized specification of the tritocerebral neuromere; in the absence of labial, the cells in this brain region do not acquire a neuronal identity and major axonal pathfinding deficits result. We have used genetic rescue experiments to investigate the functional equivalence of the Drosophila Hox gene products in the specification of the tritocerebral neuromere. Using the Gal4-UAS system, we first demonstrate that the labial mutant brain phenotype can be rescued by targeted expression of the Labial protein under the control of CNS-specific labial regulatory elements. We then show that under the control of these CNS-specific regulatory elements, all other Drosophila Hox gene products, except Abdominal-B, are able to efficiently replace Labial in the specification of the tritocerebral neuromere. We also observe a correlation between the rescue efficiency of the Hox proteins and the chromosomal arrangement of their encoding loci. Our results indicate that, despite considerably diverged sequences, most Hox proteins are functionally equivalent in their ability to replace Labial in the specification of neuronal identity. This suggests that in embryonic brain development, differences in Hox gene action rely mainly on cis-acting regulatory elements and not on Hox protein specificity.

scholarly journals Homeotic gene action in embryonic brain development of Drosophila

Development ◽  
1998 ◽  
Vol 125 (9) ◽  
pp. 1579-1589 ◽  
Author(s):  
F. Hirth ◽  
B. Hartmann ◽  
H. Reichert
Keyword(s):  
Brain Development ◽  
Gene Action ◽  
Ectopic Expression ◽  
Homeotic Gene ◽  
Homeotic Genes ◽  
Embryonic Brain ◽  
Loss Of Function ◽  
Neuronal Markers ◽  
Mutant Cells ◽  
Embryonic Brain Development

Studies in vertebrates show that homeotic genes are involved in axial patterning and in specifying segmental identity of the embryonic hindbrain and spinal cord. To gain further insights into homeotic gene action during CNS development, we here characterize the role of the homeotic genes in embryonic brain development of Drosophila. We first use neuroanatomical techniques to map the entire anteroposterior order of homeotic gene expression in the Drosophila CNS, and demonstrate that this order is virtually identical in the CNS of Drosophila and mammals. We then carry out a genetic analysis of the labial gene in embryonic brain development. Our analysis shows that loss-of-function mutation and ubiquitous overexpression of labial results in ectopic expression of neighboring regulatory genes. Furthermore, this analysis demonstrates that mutational inactivation of labial results in regionalized axonal patterning defects which are due to both cell-autonomous and cell-nonautonomous effects. Thus, in the absence of labial, mutant cells are generated and positioned correctly in the brain, but these cells do not extend axons. Additionally, extending axons of neighboring wild-type neurons stop at the mutant domains or project ectopically, and defective commissural and longitudinal pathways result. Immunocytochemical analysis demonstrates that cells in the mutant domains do not express neuronal markers, indicating a complete lack of neuronal identity. An alternative glial identity is not adopted by these mutant cells. Comparable effects are seen in Deformed mutants but not in other homeotic gene mutants. Our findings demonstrate that the action of the homeotic genes labial and Deformed are required for neuronal differentiation in the developing brain of Drosophila.

scholarly journals Pbx raises the DNA binding specificity but not the selectivity of antennapedia Hox proteins.

1997 ◽  
Vol 17 (8) ◽  
pp. 4696-4706 ◽  
Author(s):  
S T Neuteboom ◽  
C Murre
Keyword(s):  
Dna Binding ◽  
Binding Site ◽  
Binding Sites ◽  
Consensus Sequence ◽  
Binding Specificity ◽  
Selection Strategy ◽  
Gene Products ◽  
Hox Proteins ◽  
Hox Gene ◽  
Dna Binding Specificity

We have used a binding site selection strategy to determine the optimal binding sites for Pbx proteins by themselves and as heterodimeric partners with various Hox gene products. Among the Pbx proteins by themselves, only Pbx3 binds with high affinity, as a monomer or as a homodimer, to an optimal binding site, TGATTGATTTGAT. An inhibitory domain located N terminal of the Pbx1 homeodomain prevents intrinsic Pbx1 binding to this sequence. When complexed with Hoxc-6, each of the Pbx gene products binds the same consensus sequence, TGATTTAT, which differs from the site bound by Pbx3 alone. Three members of the Antennapedia family, Hoxc-6, Hoxb-7, and Hoxb-8, select the same binding site in conjunction with Pbx1. The affinities of these proteins as heterodimeric partners with Pbx1 for the selected optimal binding site are similar. However, the binding specificity of Hox proteins for optimal binding sites is increased, compared to nonspecific DNA, in the presence of Pbx proteins. Thus, while cooperative DNA binding involving heterodimers of Pbx and Hox gene products derived from members within the Antennapedia family does not increase binding site selectivity, DNA binding specificity of the Hox gene products is significantly enhanced in the presence of Pbx.

scholarly journals Genetic and environmental control of a continuous trait, Abnormal abdomen, in Drosophila melanogaster

1973 ◽  
Vol 22 (1) ◽  
pp. 37-50 ◽  
Author(s):  
Ralph Hillman
Keyword(s):  
Protein Synthesis ◽  
Gene Action ◽  
Environmental Control ◽  
Major Gene ◽  
Mutant Phenotype ◽  
Secondary Effect ◽  
Gene Products ◽  
Mutant Genotype ◽  
Developmental Effect ◽  
Number Of Factors

SUMMARYThe mutant phenotype Abnormal abdomen is under the control of a major gene, A53g located distally on the X chromosome. The phenotypic abnormalities are a result of the developmental interaction between this major gene and a modifier system associated with the residual genotype. The primary developmental effect of this mutant genotype is an interference with adult histoblast differentiation resulting in a raggedness or loss of tergite material due to the changes in the formation of the adult abdominal hypoderm. A secondary effect is an interference with middorsal fusion of the histoblasts.The developmental effect of the genotype is influenced by a number of factors which include crowding, humidity, temperature, and the age of the culture. The mutant phenotype is due to an interaction of the major gene and the modifier system in association with these environmental factors. Gene action in relation to the final phenotype is postulated to be a two-step affair. The first is an increase in protein synthesis under the influence of the modifier system; and the second is the reaction of the histoblast, under the influence of the major gene, to this increase in protein synthesis during its differentiation into adult hypoderm. The function of the environment in this sequence of developmental reactions is postulated to be in its control of the utilization of the increased protein associated with the action of the enhancer genes. This hypothesis is discussed in terms of (1) the production and utilization of gene products and of (2) the regulation of development in terms of this production and utilization in a balanced developmental system.

scholarly journals A Genetic Screen of the Drosophila X Chromosome for Mutations That Modify Deformed Function

Genetics ◽  
1998 ◽  
Vol 150 (4) ◽  
pp. 1497-1511 ◽  
Author(s):  
Brian Florence ◽  
William McGinnis
Keyword(s):  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Cell Signaling ◽  
X Chromosome ◽  
Adaptor Protein ◽  
Genetic Screen ◽  
The Other ◽  
Homeotic Gene ◽  
Hox Proteins ◽  
Hox Gene

Abstract We have screened the Drosophila X chromosome for genes whose dosage affects the function of the homeotic gene Deformed. One of these genes, extradenticle, encodes a homeodomain transcription factor that heterodimerizes with Deformed and other homeotic Hox proteins. Mutations in the nejire gene, which encodes a transcriptional adaptor protein belonging to the CBP/p300 family, also interact with Deformed. The other previously characterized gene identified as a Deformed interactor is Notch, which encodes a transmembrane receptor. These three genes underscore the importance of transcriptional regulation and cell-cell signaling in Hox function. Four novel genes were also identified in the screen. One of these, rancor, is required for appropriate embryonic expression of Deformed and another homeotic gene, labial. Both Notch and nejire affect the function of another Hox gene, Ultrabithorax, indicating they may be required for homeotic activity in general.

Patterning the ascidian nervous system: structure, expression and transgenic analysis of the CiHox3 gene

Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4737-4748 ◽  
Author(s):  
A. Locascio ◽  
F. Aniello ◽  
A. Amoroso ◽  
M. Manzanares ◽  
R. Krumlauf ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hox Genes ◽  
Regional Identity ◽  
Regulatory Elements ◽  
System Structure ◽  
Anteroposterior Patterning ◽  
Hox Gene ◽  
The Central Nervous System ◽  
Group 3

Hox genes play a fundamental role in the establishment of chordate body plan, especially in the anteroposterior patterning of the nervous system. Particularly interesting are the anterior groups of Hox genes (Hox1-Hox4) since their expression is coupled to the control of regional identity in the anterior regions of the nervous system, where the highest structural diversity is observed. Ascidians, among chordates, are considered a good model to investigate evolution of Hox gene, organisation, regulation and function. We report here the cloning and the expression pattern of CiHox3, a Ciona intestinalis anterior Hox gene homologous to the paralogy group 3 genes. In situ hybridization at the larva stage revealed that CiHox3 expression was restricted to the visceral ganglion of the central nervous system. The presence of a sharp posterior boundary and the absence of transcript in mesodermal tissues are distinctive features of CiHox3 expression when compared to the paralogy group 3 in other chordates. We have investigated the regulatory elements underlying CiHox3 neural-specific expression and, using transgenic analysis, we were able to isolate an 80 bp enhancer responsible of CiHox3 activation in the central nervous system (CNS). A comparative study between mouse and Ciona Hox3 promoters demonstrated that divergent mechanisms are involved in the regulation of these genes in vertebrates and ascidians.

Expression of HOX gene products in normal and abnormal trophoblastic tissue

2003 ◽  
Vol 90 (3) ◽  
pp. 512-518 ◽  
Author(s):  
Lawrence S Amesse ◽  
Robert Moulton ◽  
Yue Mei Zhang ◽  
Teresa Pfaff-Amesse
Keyword(s):  
Gene Products ◽  
Hox Gene ◽  
Trophoblastic Tissue

Morphologic and neurochemical studies of embryonic brain development in murine trisomy 16

1984 ◽  
Vol 15 (2) ◽  
pp. 155-166 ◽  
Author(s):  
Harvey S. Singer ◽  
Michael Tiemeyer ◽  
John C. Hedreen ◽  
John Gearhart ◽  
Joseph T. Coyle
Keyword(s):  
Brain Development ◽  
Embryonic Brain ◽  
Trisomy 16 ◽  
Embryonic Brain Development

Transducing positional information to the Hox genes: critical interaction of cdx gene products with position-sensitive regulatory elements

Development ◽  
1998 ◽  
Vol 125 (22) ◽  
pp. 4349-4358 ◽  
Author(s):  
J. Charite ◽  
W. de Graaff ◽  
D. Consten ◽  
M.J. Reijnen ◽  
J. Korving ◽  
...  
Keyword(s):  
Binding Sites ◽  
Hox Genes ◽  
Regulatory Element ◽  
Ectopic Expression ◽  
Positional Information ◽  
Regulatory Elements ◽  
Gene Products ◽  
Anteroposterior Patterning

Studies of pattern formation in the vertebrate central nervous system indicate that anteroposterior positional information is generated in the embryo by signalling gradients of an as yet unknown nature. We searched for transcription factors that transduce this information to the Hox genes. Based on the assumption that the activity levels of such factors might vary with position along the anteroposterior axis, we devised an in vivo assay to detect responsiveness of cis-acting sequences to such differentially active factors. We used this assay to analyze a Hoxb8 regulatory element, and detected the most pronounced response in a short stretch of DNA containing a cluster of potential CDX binding sites. We show that differentially expressed DNA binding proteins are present in gastrulating embryos that bind to these sites in vitro, that cdx gene products are among these, and that binding site mutations that abolish binding of these proteins completely destroy the ability of the regulatory element to drive regionally restricted expression in the embryo. Finally, we show that ectopic expression of cdx gene products anteriorizes expression of reporter transgenes driven by this regulatory element, as well as that of the endogenous Hoxb8 gene, in a manner that is consistent with them being essential transducers of positional information. These data suggest that, in contrast to Drosophila Caudal, vertebrate cdx gene products transduce positional information directly to the Hox genes, acting through CDX binding sites in their enhancers. This may represent the ancestral mode of action of caudal homologues, which are involved in anteroposterior patterning in organisms with widely divergent body plans and modes of development.

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