transcription factor - zinc finger transcriptional repressor - gap gene required later for proper generation of neural sublineages - enriched in the larval eye and controls photoreceptor differentiation by promoting Rh5 and Rh6 expression
402, 256 (aa)
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Comment: reported as procephalic ectoderm anlage in statu nascendi
Comment: reported as procephalic ectoderm anlage in statu nascendi
Comment: reported as dorsal/lateral sensory complexes
Nascent Kr transcripts can be detected as early as cycle 7, but do not become numerous enough to be visible on whole-embryo imaging until cycle 10.
The Kr transcript is expressed in the early embryo in a central stripe spanning from 40% to 60% egg length.
Kr transcript is first expressed in early blastoderm stage embryos in a broad central stripe. Late blastoderm stage embryos have an additional anterior stripe (80% egg length) and posterior stripe (90-100% egg length) of Kr transcript expression. By early gastrulation, the anterior stripe resolves into two stripes, and the central band into four stripes of differing intensities.
Kr is expressed in the middle of the blastoderm embryo from approximately 39-57% egg length.
In germ band retracted embryos, Kr transcripts are detected in the embryonic brain, as well as the precursor lateral muscle cells, significant levels are also detected in developing neural tissue.
The primary Kr transcript is most abundant in 2-5 hour embryos, but transcripts are detected through pupal stages at lower levels.
Kr is expressed in the larval photoreceptors but is absent from the photoreceptors of adult ocelli. It is expressed in all larval photoreceptor precursors throughout embryogenesis. Thereafter, it is maintained in both photoreceptor subtypes (Rh5-expressing and Rh6-expressing) during larval stages.
Kr is differentially expressed in the LAMPs (lateral adult muscle precursor cells). It is expressed strongly in the anterior LAMP but not in the posterior LAMP.
Kr is expressed in Bolwig organ precursors beginning in embryonic stage 12 and continuing through the larval stages.
Protein is detected in a subset of myoblasts, the founder cells, in stage 13 embryos. As additional cells are recruited to the developing myotubes expression is observed in these clusters corresponding to fusing myotubes.
The Malpighian tubule cells are alocated and evert from the embryonic hindgut during extended germband stage. From this stage on protein is detected in the tubule cells.
In blastoderm stageembryos, Kr protein is localized to the dorsal and ventral periphery, in aband ranging from 10-12 nuclei dorsally and 14-16 nuclei ventrally (40-60% egglength). Staining is highest in the central domain, and fades in a gradedfashion towards the edges of this "Kr domain".
GBrowse - Visual display of RNA-Seq signalsView Dmel\Kr in GBrowse 2
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Source for identity of: Kr CG3340
Haploinsufficient locus (not associated with strong haplolethality or haplosterility).
Kr is found to have three specific regions within the coding sequence that are highly conserved during Drosophila speciation.
KrT95D is a putative Kr target gene. Expression patterns of KrT95D and Kr suggest that Kr activity is necessary to activate KrT95D expression in the VO5 muscle precursors, consistent with recent results indicating that Kr activity is necessary for specification of a subset of muscles and their proper innervation during embryogenesis.
Kr is not required in the mesoderm for the segregation of a normal pattern of muscle founder cells, or to initiate patterns of gene expression in these founders. It is required for the maintenance of normal patterns of gene expression in the precursors that the founders form, and for the acquisition of proper muscle identity during embryogenesis. Gain and loss of Kr expression in sibling founder cells is sufficient to switch the cells, and the muscle they give rise to, between alternative cell fates.
The Kr and sna proteins function as short range repressors, which can mediate either quenching or direct repression of a transcription complex, depending on the location of repressor sites. Local quenching and dominant repression require close linkage of the repressor with either upstream activators or the transcription complex.
Kr is expressed in neural precursor cells, neurons and glial cells at different stages of neurogenesis and Kr mutants develop aberrant peripheral and central nervous systems. Phenotypic analysis of rescued embryos (by a Kr minigene) indicates that Kr expression in the nervous system is functionally required for establishing particular neural and glial fates.
Kr monomer (the activator) interacts with TfIIB, Kr dimers do not (FBrf0082559). Kr dimers engage in protein-protein interaction with TfIIEβ (FBrf0082559). Kr monomer-dimer transition alters Krs ability to interact with the general transcription machinery (FBrf0082559).
Transcription factors hb and kni can associate with Kr in vitro and they interact functionally with Kr-dependent target gene expression mediated by a single Kr-binding site close to an heterologous promoter in Schneider cells.
Kr-dependent control of transcription involves functional interactions with components of the basal RNA polymerase II transcription machinery.
The region of Kr important for transcriptional repression has been fine mapped and is defined by a minimal 31 amino acid motif rich in Ala and Gln residues.
Comparisons of early development to that in other insects have revealed conservation of some aspects of development, as well as differences that may explain variations in early patterning events.
Ectopic ttk expression has no effect on expression of Kr and hb.
Expression of prd depends on activation by gap gene hb, Kr, kni and gt products. Primary pair rule gene products act primarily in subsequent modulation rather than activation of prd stripes. Factors activating prd expression in the pair rule mode interact with those activating it along the dorso-ventral axis.
Examination of conserved tracts in the D.virilis and D.melanogaster h gene promoters identified potential ftz-f1, Kr and gt binding sites. Kr and gt products establish the anterior and posterior borders of h stripe 5, respectively, through spatial repression.
The Kr gene product selectively represses transcription activated by a glutamine rich activator but not by an acidic activator. This indicates that the Kr protein quenches transcription due to specific protein-protein interactions between Kr protein and part of the transcriptional apparatus mediating stimulation by a glutamine-rich activator.
Phenotypic rescue of Kr mutants by P-element mediated transformation of a Kr minigene demonstrates that the Kr gene product is required for nervous system development and its activity is driven by the neuro-specific enhancer elements which are lacking in the transgenic embryos.
Kr gene product is able to form homodimers through sequences located within the C terminus, termed C64KR sequences: when fused to separated functional parts of the yeast transcription factor GAL4 they reconstituted a functional transcriptional activator on dimerization in vivo. Results of in vitro experiments suggest that Kr monomer product is a transcriptional activator, whereas at higher concentrations it forms a homodimer that acts as a repressor acting on the same target sites as recognised by the activator.
Mutations affect eye morphology.
In vitro footprinting of bacterially expressed kni and tll protein found one strong kni binding site and seven tll binding sites in a 730 bp fragment of the Kr promoter. Binding studies demonstrate that each of the proteins can bind but their binding is mutually exclusive. Ecol\lacZ reporter gene constructs carrying 16 bp fragment of the overlapping kni and bcd protein binding sites demonstrated that expression mediated by the 16 bp element is dependent on bcd activity, kni represses expression by competitive binding.
Kr acts downstream of ct in the Malpighian tubule regulatory pathway. Kr activity is required for cad expression in the tubules.
Kr activity required for neurons to differentiate into Bolwig organs and for the fasciculation of the Bolwig nerve.
The gene products of bcd, hb, Kr and gt all bind within the 480bp region that is necessary and sufficient for the expression of eve stripe 2. Forming the posterior border of the stripe involves a delicate balance between Kr repressor and bcd activator.
Sequence alignments of orthologous fragments of hb, Kr and sna from a variety of arthropods and other phyla show that amino acid differences are not normally correlated with evolutionary distance between respective species. Amino acids directly involved in DNA binding are the most conserved, and binding specificity of a hb finger from different species is not changed.
Kr has a direct negative effect on gt expression.
Ecol\lacZ reporter gene constructs carrying Kr promoter deletions have identified a 142bp core sequence (the Kr730 element) within the cis-acting control element (CD1) which mediates gene expression in a central region of the embryo in response to hb and bcd activities.
Transcriptional analysis of Kr deletion constructs has identified a 44bp fragment from -31bp to +13bp with significant promoter activity.
Kr is a strong repressor of gt in the embryo.
Low amounts of Kr expression lead to transcriptional activation, whereas high amounts result in repression. Distinct portions of Kr protein, other than the DNA-binding domain, are required for gene activation and repression, suggesting that Kr itself can act as a concentration- dependent positive and negative regulator of transcription.
Zygotically active locus involved in the terminal developmental program in the embryo.
Kr mutants exhibit deletions of the thorax and anterior abdomen.
The regulatory relationships of Kr with respect to its role in the development of the Malpighian tubules differs from its interactions with the segmentation process.
Ubx, Kr and eve expression are altered in fs(1)h mutant embryos. Defects in the segmental organisation in fs(1)h-deficient progeny are mediated primarily, but not exclusively, through a restriction in the Kr expression domain.
Characterisation of the crude RNA polymerase II transcription system using transcription initiation of the Kr promoter.
The transcriptional repression function of Kr maps to an alanine-rich amino terminal region of the protein (between amino acids 26 to 110).
Kr exhibits a homeotic function in addition to its role as a segmentation gene and is involved in separating hindgut and Malpighian tubule cells and in the elongation process as well.
An investigation of the role of gap genes in expression from Ubx and Antp promoters in the blastoderm embryo reveals that a unique combination of gap genes and pair rule genes is required for their initial activation.
Mutations in Kr alter gt expression in the posterior of the embryo.
Genetic analysis demonstrates that the effect of the gap gene product Kr on homeotic gene expression in the visceral mesoderm is indirect and mediated by the genes that establish parasegment borders, eve and ftz.
Kr activity is required for the establishment of the Antp T3 domain. Kr is involved in restricting Abd-B products within the A8--A9 domain.
Mutant embryos exhibit a slight increase in the number of Dfd expressing cells in ventral and lateral positions.
Involved in functions related to that of tll.
The wild-type allele of Kruppel controls the development of the thoracic and abdominal segments of Drosophila; homozygous mutants show a gap in the larval pattern in these regions (Nusslein-Volhard and Wieschaus, 1980; Knipple et al., 1987). Kr/+ adult sometimes has thoracic malformation; a leg or a wing may be absent; penetrance low. Heterozygous larvae show small defects in denticle bands of thorax and abdomen as do heterozygous deficiencies for Kr; penetrance about 80%. Homozygotes are embryonic lethal. Kr1 homozygotes exhibit shortened germ band of but three to four segments with three to four tracheal pits; visible beginning at 7h of embryogenesis; head and gnathal segments apparently normal. At later stages only three to four abdominal and thoracic segments clearly visible; normal telson and segments 8 and 7 followed by enlarged sixth, a rudimentary fifth and apparently mirror image sixth segment. Weak and intermediate mutant alleles lack the mirror-image duplications (Gaul and Jackle, 1987b). Ventral chain of ganglia disconnected; tracheal system defective; Malpighian tubules missing; salivary glands normal. Homozygotes for hypomorphic alleles display more nearly complete segmentation. Homozygous Minute+ Kr clones develop normally in all parts of adult cuticle of M/+ flies. Metamorphic potential of Kr/Kr embryos cultured in female abdomens restricted in that wing-disc-derived structures not observed. Germline clones of homozygous Kr cells capable of normal oogenesis; no maternal effect of Kr+ observed. Requirement for Kr+ function apparently restricted to early embryogenesis. Kr affects ftz producing abnormal intensity and spacing of ftz stripes in thorax and anterior abdomen (Carroll and Scott, 1986).