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C Q Doe

Publications and source records attributed to C Q Doe.

At least 55 records · Page 3Linked to original sources
PubMed1995

The role of the cell cycle and cytokinesis in regulating neuroblast sublineage gene expression in the Drosophila CNS.

The precise temporal control of gene expression is critical for specifying neuronal identity in the Drosophila central nervous system (CNS). A particularly interesting class of genes are those expressed at stereotyped times during the cell lineage of identified neural precursors (neuroblasts): these are termed 'sublineage' genes. Although sublineage gene function is vital for CNS development, the temporal regulation of this class of genes has not been studied. Here we show that four genes (ming, even-skipped, unplugged and achaete) are expressed in specific neuroblast sublineages. We show that these neuroblasts can be identified in embryos lacking both neuroblast cytokinesis and cell cycle progression (string mutants) and in embryos lacking only neuroblast cytokinesis (pebble mutants). We find that the unplugged and achaete genes are expressed normally in string and pebble mutant embryos, indicating that temporal control is independent of neuroblast cytokinesis or counting cell cycles. In contrast, neuroblasts require cytokinesis to activate sublineage ming expression, while a single, identified neuroblast requires cell cycle progression to activate even-skipped expression. These results suggest that neuroblasts have an intrinsic gene regulatory hierarchy controlling unplugged and achaete expression, but that cell cycle- or cytokinesis-dependent mechanisms are required for ming and eve CNS expression.

Animals↗
PubMed1995

Asymmetric localization of numb autonomously determines sibling neuron identity in the Drosophila CNS.

The central nervous system (CNS) represents an excellent model system for examining how a multitude of unique cell fates are specified. We find that asymmetric localization of the numb protein autonomously controls a binary cell fate decision in the Drosophila CNS. The simplest lineage in the Drosophila CNS is that of the MP2 precursor: it divides unequally to generate the dMP2 and vMP2 neurons. Both are interneurons but project in different directions: dMP2 projects its axon posteriorly while vMP2 projects anteriorly. During MP2 mitosis, numb is localized into dMP2 and excluded from vMP2. Loss of numb transforms dMP2 into vMP2, whereas ectopic numb produces the opposite transformation of vMP2 into dMP2. Thus, numb is asymmetrically localized in the dividing MP2 and is necessary and sufficient to autonomously specify dMP2 neuronal identity.

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PubMed1995

Evolution of neuroblast identity: seven-up and prospero expression reveal homologous and divergent neuroblast fates in Drosophila and Schistocerca.

In the Drosophila CNS, early neuroblast formation and fate are controlled by the pair-rule class of segmentation genes. The distantly related Schistocerca (grasshopper) embryo has a similar arrangement of neuroblasts, despite lack of known pair-rule gene function. Does divergent pair-rule gene function lead to different neuroblast identities, or can different patterning mechanisms produce homologous neuroblasts? We use four molecular markers to compare Drosophila and Schistocerca neuroblast identity: seven-up, prospero, engrailed, and fushi-tarazu/Dax. In both insects some early-forming neuroblasts share key features of neuroblast identity (position, time of formation, and temporally accurate gene expression); thus, different patterning mechanisms can generate similar neuroblast fates. In contrast, several later-forming neuroblasts show species-specific differences in position and/or gene expression; these neuroblast identities seem to have diverged, suggesting that evolution of the insect central nervous system can occur through changes in embryonic neuroblast identity.

Amino Acid Sequence↗
PubMed1994

Sp1/egr-like zinc-finger protein required for endoderm specification and germ-layer formation in Drosophila.

Much of our present knowledge of the biological processes involved in pattern formation in Drosophila is derived from segmentation analysis. Comparatively little is known about the genetic requirement and mechanisms underlying the formation and separation of germ layers by morphogenetic movements during gastrulation. Here we show that the Drosophila gene huckebein (hkb), a member of the gap-gene class of segmentation genes, is required for germ-layer formation at blastoderm. Absence of the hkb product, an Sp1/egr-like zinc-finger protein, causes the ectodermal and mesodermal primordia to expand at the expense of endoderm anlagen. Conversely, ectopic expression of hkb inhibits the formation of the major gastrulation fold which gives rise to the mesoderm and prevents normal segmentation in the ectoderm. Thus, hkb is necessary for endoderm development and its activity defines spatial limits within the blastoderm embryo in which the germ layers are established.

Amino Acid Sequence↗
PubMed1994

RK2, a glial-specific homeodomain protein required for embryonic nerve cord condensation and viability in Drosophila.

We report the identification of RK2, a glial-specific homeodomain protein. RK2 is localized to the nucleus of virtually all embryonic and imaginal glial cells, with the exception of midline glia. Embryos mutant for the gene encoding RK2 are embryonic lethal but normal for early gliogenesis (birth, initial divisions and migration of glia) and axonogenesis (neuronal pathfinding and fasciculation). However, later in development, there are significantly fewer longitudinal glia that are spatially disorganized; in addition, there is a slight disorganization of axon fascicles and a defective nerve cord condensation. This suggests that RK2 is not required for early glial determination, but rather for aspects of glial differentiation or function that are required for embryonic viability.

Amino Acid Sequence↗
PubMed1993

Neuroblast specification and formation regulated by wingless in the Drosophila CNS.

The Drosophila central nervous system (CNS) develops from a heterogeneous population of neural stem cells (neuroblasts), yet the genes regulating neuroblast determination remain unknown. The segmentation gene wingless is regionally expressed in the neuroectoderm from which neuroblasts develop. A conditional wingless mutation is used to inactivate CNS function without affecting segmentation. The stripe of wingless-expressing neuroectoderm generates apparently normal neuroblasts after wingless inactivation; however, adjacent anterior and posterior neuroectoderm requires wingless nonautonomously for subsequent neuroblast determination and formation. Loss of wingless results in the absence or duplication of identified neuroblasts, highlighting its role in generating neuroblast diversity in the CNS.

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PubMed1993

Identification and cell lineage of individual neural precursors in the Drosophila CNS.

The Drosophila CNS is complex enough to serve as a model for many of the molecular, cellular and developmental functions of the vertebrate CNS, yet simple enough for single-cell analysis. Recent advances have provided molecular markers that allow most Drosophila CNS precursors to be uniquely identified, as well as methods for determining the complete cell lineage of each precursor. A detailed understanding of wild-type neurogenesis, combined with existing molecular genetic techniques, should provide insight into the fundamental mechanisms that generate neuronal and glial diversity.

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PubMed1993

Prox 1, a prospero-related homeobox gene expressed during mouse development.

Prox 1, a likely mouse homologue of the Drosophila homeobox gene prospero has been cloned and its expression pattern analyzed during development. In Drosophila, prospero is expressed in the developing CNS, lens-secreting cone cells of the eye, and midgut. In the mouse, Prox 1 is expressed in many of the same tissues: young neurons of the subventricular region of the CNS, developing eye lens and pancreas. Expression is also detected in the developing liver and heart, as well as transiently in the skeletal muscles. The similarities in protein sequence and expression patterns between the mouse and fly cognate genes suggest that Prox 1 may play, among others, a fundamental role in early development of the murine CNS.

Amino Acid Sequence↗
PubMed1992

Molecular markers for identified neuroblasts and ganglion mother cells in the Drosophila central nervous system.

The first step in generating cellular diversity in the Drosophila central nervous system is the formation of a segmentally reiterated array of neural precursor cells, called neuroblasts. Subsequently, each neuroblast goes through an invariant cell lineage to generate neurons and/or glia. Using molecular lineage markers, I show that (1) each neuroblast forms at a stereotyped time and position; (2) the neuroblast pattern is indistinguishable between thoracic and abdominal segments; (3) the development of individual neuroblasts can be followed throughout early neurogenesis; (4) gene expression in a neuroblast can be reproducibly modulated during its cell lineage; (5) identified ganglion mother cells form at stereotyped times and positions; and (6) the cell lineage of four well-characterized neurons can be traced back to two identified neuroblasts. These results set the stage for investigating neuroblast specification and the mechanisms controlling neuroblast cell lineages.

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PubMed1992

ming is expressed in neuroblast sublineages and regulates gene expression in the Drosophila central nervous system.

Cell diversity in the Drosophila central nervous system (CNS) is primarily generated by the invariant lineage of neural precursors called neuroblasts. We used an enhancer trap screen to identify the ming gene, which is transiently expressed in a subset of neuroblasts at reproducible points in their cell lineage (i.e. in neuroblast 'sublineages'), suggesting that neuroblast identity can be altered during its cell lineage. ming encodes a predicted zinc finger protein and loss of ming function results in precise alterations in CNS gene expression, defects in axonogenesis and embryonic lethality. We propose that ming controls cell fate within neuroblast cell lineages.

Amino Acid Sequence↗
PubMed1991

The prospero gene specifies cell fates in the Drosophila central nervous system.

The molecular mechanisms used to generate neuronal diversity are largely unknown. To identify genes controlling cell fate in the Drosophila central nervous system, we screened for mutations that alter expression of homeobox genes in the developing central nervous system (indicating changes in cell fates). We also screened "enhancer trap" lines to identify genes expressed in neuronal stem cells (neuroblasts). The prospero gene was discovered in both screens. prospero is expressed in a subset of neuroblasts, sensory neuron precursors, and identified glial precursors. It is not expressed in neurons. Neuroblasts lacking prospero function generate abnormal cell lineages, producing incorrectly specified progeny that differentiate into neurons showing axon pathfinding defects. prospero is therefore a novel type of gene expressed in neuroblasts and known to specify neuronal fate.

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PubMed1991

The prospero gene encodes a divergent homeodomain protein that controls neuronal identity in Drosophila.

The Drosophila central nervous system (CNS) develops from a population of stem cells called neuroblasts; each neuroblast goes through an invariant cell lineage to produce a characteristic family of neurons or glia. We are interested in the molecular mechanisms controlling neuroblast cell lineage. Recently we identified the prospero (pros) gene, which is expressed in embryonic neuroblasts. Loss of pros function results in aberrant expression of the homeobox genes fushi tarazu, even-skipped and engrailed in a subset of neuroblast progeny, suggesting that pros plays an early and fundamental role in the specification of neuronal fate (Doe et al. 1991). Here we show that the pros gene encodes a highly divergent homeodomain. The homeodomain contains several of the most conserved amino acids characteristic of known homeodomains, yet it is considerably less basic than previously identified homeodomains. These data are consistent with a model in which pros controls neuroblast cell lineages by regulating gene expression.

Amino Acid Sequence↗
PubMed1990

The origins of cell diversity in the insect central nervous system.

There are thousands of unique neurons and many types of glia in the insect central nervous system. How is this cell diversity generated? Neurogenesis begins with the delamination and enlargement of individual cells of the ventral ectoderm to form a stereotyped array of neuroblasts. Every neuroblast divides asymmetrically to generate a chain of approximately 10 smaller progeny, each of which produces a pair of neurons. Ablation, transplantation and in vitro culture experiments illuminate the role of cell interactions and cell lineage during neurogenesis, and genetic approaches in Drosophila are beginning to provide insight into the molecular mechanisms controlling these events.

Animals↗
PubMed1988

Control of neuronal fate by the Drosophila segmentation gene even-skipped.

The central nervous system (CNS) contains a remarkable diversity of cell types. The molecular basis for generating this neuronal diversity is poorly understood. Much is known, however, about the regulatory genes which control segmentation and segment identity during early Drosophila embryogenesis. Interestingly, most of the segmentation and homoeotic genes in Drosophila, as well as many of their vertebrate homologues, are expressed during the development of the nervous system (for example, ref. 3). Are these genes involved in specifying the identity of individual neurons during neurogenesis, just as they specify the identity of cells during segmentation? We previously described the CNS expression of the segmentation gene fushi tarazu (ftz) and showed that ftz CNS expression is involved in the determination of an identified neuron. Here we show that another segmentation gene, even-skipped (eve), is expressed in a different but overlapping subset of neurons. Temperature-sensitive inactivation of the eve protein during neurogenesis alters the fate of two of these neurons. Our results indicate that the nuclear protein products of the eve and ftz segmentation genes are components of the mechanism controlling cell fate during neuronal development.

Animals↗
PubMed1988

Expression and function of the segmentation gene fushi tarazu during Drosophila neurogenesis.

Segmentation genes control cell identities during early pattern formation in Drosophila. One of these genes, fushi tarazu (ftz), is now shown also to control cell fate during neurogenesis. Early in development, ftz is expressed in a striped pattern at the blastoderm stage. Later, it is transiently expressed in a specific subset of neuronal precursor cells, neurons (such as aCC, pCC, RP1, and RP2), and glia in the developing central nervous system (CNS). The function of ftz in the CNS was determined by creating ftz mutant embryos that express ftz in the blastoderm stripes but not in the CNS. In the absence of ftz CNS expression, some neurons appear normal (for example, the aCC, pCC, and RP1), whereas the RP2 neuron extends its growth cone along an abnormal pathway, mimicking its sibling (RP1), suggesting a transformation in neuronal identity.

Animals↗
PubMed1986

Guidance of neuronal growth cones in the grasshopper embryo. IV. Temporal delay experiments.

In the previous 3 papers, we demonstrated that neuronal growth cones display selective affinities for both specific axonal and glial pathways in the grasshopper embryo; for example, the pCC growth cone selectively recognizes the MP1/dMP2 axons, while the aCC growth cone selectively recognizes the U axons and a specific glial cell (the segment boundary cell). We were interested in further testing the temporal specificity of these affinities. To address this issue, we performed specific temporal transplant experiments by using a laser microbeam in ovo to ablate the neuronal precursor cell, neuroblast (NB) 1-1, that generates the aCC and pCC neurons. Neighboring ectodermal cells regulate and replace the ablated NB 1-1; the new NB 1-1 then generates the aCC and pCC neurons with a temporal delay of 10-20 hr (2-4% of development), depending upon the experimental paradigm. The results of these temporal delay experiments further demonstrate the selective affinities of the aCC and pCC growth cones for specific axonal and glial surfaces and confirm that these specificities are absolute and not hierarchical. Furthermore, they suggest that precise timing is not important; both the pCC and aCC growth cones are able to selectively recognize their appropriate axonal and glial pathways after delays of 10-20 hr despite being confronted with the surfaces of many additional axons and pathways.

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