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Biomedical subjects

J P Kumar

Publications and source records attributed to J P Kumar.

14 recordsLinked to original sources
PubMed2001

Perturbing nuclear transport in Drosophila eye imaginal discs causes specific cell adhesion and axon guidance defects.

To study nucleocytoplasmic transport during multicellular development, we developed a sensitive nuclear protein import assay in living blastoderm embryos. We show that dominant negative truncations of the human nuclear transport receptor karyopherinbeta/Importinbeta (DNImpbeta) disrupt mRNA export and protein import in Drosophila. To test the sensitivity of different developmental processes to nuclear trafficking perturbations, we expressed DNImpbeta behind the morphogenetic furrow of the eye disc, at a time when photoreceptors are patterned and project their axons to the brain. DNImpbeta expression does not disrupt the correct specification of different photoreceptors, but causes a defect in cell adhesion that leads to some photoreceptors descending below the layer of ommatidia. The photoreceptors initially project their axons correctly to the posterior, but later their axons are unable to enter the optic stalk en route to the brain and continue to project an extensive network of misguided axons. The axon guidance and cell adhesion defects are both due to a disruption in the function of Ketel, the Drosophila ortholog of Importinbeta. We conclude that cell adhesion and axon guidance in the eye have specific requirements for nucleocytoplasmic transport, despite involving processes that occur primarily at the cell surface.

Active Transport, Cell Nucleus↗
PubMed2001

EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification.

The Drosophila compound eye is specified by the concerted action of seven nuclear factors that include Eyeless/Pax6. These factors have been called "master control" proteins because loss-of-function mutants lack eyes and ectopic expression can direct ectopic eye development. However, inactivation of these genes does not cause the presumptive eye to change identity. Surprisingly, we find that several of these eye specification genes are not coexpressed in the same embryonic cells-or even in the presumptive eye. We demonstrate that the EGF Receptor and Notch signaling pathways have homeotic functions that are genetically upstream of the eye specification genes, and show that specification occurs much later than previously thought-not during embryonic development but in the second larval stage.

Animal Structures↗
PubMed2001

Eye specification in Drosophila: perspectives and implications.

The discovery that Drosophila eyeless is homologous to vertebrate Pax6 produced enormous interest in eye specification and a reappraisal of eye evolution. While the transcription factor Eyeless/Pax6 is necessary and in some circumstances sufficient to induce eye development the simple story of eye specification has become more epic than haiku. At least seven other nuclear proteins act with Eyeless/Pax6 to induce the eye and, furthermore, extrinsic developmental signals are required. Some striking similarities between later events of retinal patterning in vertebrates and insects have led to a deeper debate on the evolutionary path to these apparently quite different organs.

Animals↗
PubMed2001

Expression of evolutionarily conserved eye specification genes during Drosophila embryogenesis.

Eye specification in Drosophila is thought be controlled by a set of seven nuclear factors that includes the Pax6 homolog, Eyeless. This group of genes is conserved throughout evolution and has been repeatedly recruited for eye specification. Several of these genes are expressed within the developing eyes of vertebrates and mutations in several mouse and human orthologs are the underlying causes of retinal disease syndromes. Ectopic expression in Drosophila of any one of these genes is capable of inducing retinal development, while loss-of-function mutations delete the developing eye. These nuclear factors comprise a complex regulatory network and it is thought that their combined activities are required for the formation of the eye. We examined the expression patterns of four eye specification genes, eyeless (ey), sine oculis (so), eyes absent (eya), and dachshund (dac) throughout all time points of embryogenesis and show that only eyeless is expressed within the embryonic eye anlagen. This is consistent with a recently proposed model in which the eye primordium acquires its competence to become retinal tissue over several time points of development. We also compare the expression of Ey with that of a putative antennal specifying gene Distal-less (Dll). The expression patterns described here are quite intriguing and raise the possibility that these genes have even earlier and wide ranging roles in establishing the head and visual field.

Animals↗
PubMed2001

Signalling pathways in Drosophila and vertebrate retinal development.

The near-catholic conservation of paired box gene 6 (Pax6) and its supporting cast of retinal determination genes throughout the animal kingdom has sparked a scientific war over the evolutionary origins of the eye. The battle pits those who support a polyphyletic history for the eye against those who argue for a common ancestor for all 'seeing' animals. Recent papers have shed light on how eyes in both vertebrates and invertebrates are patterned. New insights into the roles that signal-transduction cascades might have in determining the Drosophila melanogaster eye indicate that, like many developmental processes, eye specification is an inductive process.

Animals↗
PubMed2001

The EGF receptor and notch signaling pathways control the initiation of the morphogenetic furrow during Drosophila eye development.

The onset of pattern formation in the developing Drosophila retina begins with the initiation of the morphogenetic furrow, the leading edge of a wave of retinal development that transforms a uniform epithelium, the eye imaginal disc into a near crystalline array of ommatidial elements. The initiation of this wave of morphogenesis is under the control of the secreted morphogens Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg). We show that the Epidermal Growth Factor Receptor and Notch signaling cascades are crucial components that are also required to initiate retinal development. We also show that the initiation of the morphogenetic furrow is the sum of two genetically separable processes: (1) the 'birth' of pattern formation at the posterior margin of the eye imaginal disc; and (2) the subsequent 'reincarnation' of retinal development across the epithelium.

Animals↗
PubMed1998

Dissecting the roles of the Drosophila EGF receptor in eye development and MAP kinase activation.

A new conditional Egfr allele was used to dissect the roles of the receptor in eye development and to test two published models. EGFR function is necessary for morphogenetic furrow initiation, is not required for establishment of the founder R8 cell in each ommatidium, but is necessary to maintain its differentiated state. EGFR is required subsequently for recruitment of all other neuronal cells. The initial EGFR-dependent MAP kinase activation occurs in the furrow, but the active kinase (dp-ERK) is observed only in the cytoplasm for over 2 hours. Similarly, SEVENLESS-dependent activation results in cytoplasmic appearance of dp-ERK for 6 hours. These results suggest an additional regulated step in this pathway and we discuss models for this.

Alleles↗
PubMed1997

Rhodopsin replacement rescues photoreceptor structure during a critical developmental window.

Rhodopsin is essential for normal photoreceptor development in Drosophila (O'Tousa et al., 1989; Leonard et al., 1992; Kumar and Ready, 1995) and in mice (Humphries et al., 1997). Here we report studies in which a rhodopsin transgene is expressed at restricted stages during the development of Drosophila photoreceptors otherwise lacking rhodopsin. Substantial rescue of normal photoreceptor structure and physiology is effected by rhodopsin expression during the time of the normal onset of rhodopsin synthesis. Expression shortly before or after this critical period does not rescue these deficits. There is a critical developmental period in which rhodopsin plays its key role in photoreceptor morphogenesis.

Animals↗
PubMed1995

Rhodopsin plays an essential structural role in Drosophila photoreceptor development.

Null mutations of the Drosophila Rh1 rhodopsin gene, ninaE, result in developmental defects in the photosensitive membranes, the rhabdomeres, of compound eye photoreceptors R1-R6. In normal flies, Rh1 expression begins at about 78% of pupal life. At approximately 90% of pupal life, a specialized catacomb-like membrane architecture develops at the base of normal rhabdomeres. In ninaE null mutants, these catacombs do not form and developing rhabdomere membrane involutes into the cell as curtains of apposed plasma membrane. A filamentous cytoskeletal complex that includes F-actin and the unconventional myosin, NINAC, decorates the cytoplasmic surface of these curtains.

Animals↗
PubMed1993

Characterization of the radiation-sensitive stage in the development of the compound eye of Drosophila.

The development of the compound eye of Drosophila is particularly sensitive to irradiation during the third larval instar. Moreover, the anterioposterior location of the eye-pattern defects produced by irradiation during the third instar is correlated with the age of the larvae at the time of irradiation, as first shown by H.J. Becker. The development of the fly eye proceeds from posterior to anterior, and so these results suggest that there may be a radiation-sensitive stage in the development of the precursor cells in the eye imaginal disc of Drosophila. We show here that irradiation of third-instar Drosophila larvae with 23-30 Gy of 60Co gamma-rays produces confluent pattern disruptions in a dorsoventral stripe of eye tissue with an average width of about 8 facets along the anterioposterior axis. By measuring the time interval from irradiation to pupariation in individual larvae, we were able to determine that the posterior boundary of the radiation-sensitive region is located 0-1 columns anterior to the morphogenetic furrow in the developing eye imaginal disc. Therefore the anterior boundary of the radiation-sensitive region lies about 8-9 columns anterior to the morphogenetic furrow. These boundaries demarcate the region of the eye imaginal disc within which a specific subset of precursor cells (those that will develop into the R1, R6 and R7 photoreceptor cells, as well as the pigment and cone cells) are preparing for their final round of mitosis. Irradiation of these precursor cells would cause the death or delayed mitosis of their daughter cells within the morphogenetic furrow, while they are initiating the cellular interactions that determine cell fate in the developing eye. Irradiation of more anterior cells (i.e., at earlier stages) results in few pattern defects, presumably because the resulting cell death and delayed mitosis can be completed before the morphogenetic furrow passes.

Animals↗