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C Q Doe

Publications and source records attributed to C Q Doe.

At least 19 recordsLinked to original sources
PubMed1995

Specification of neuroblast identity in the Drosophila embryonic central nervous system by gooseberry-distal.

The Drosophila central nervous system develops from a segmentally reiterated array of 30 unique neural precursors, called neuroblasts. Each neuroblast goes through a stereotyped cell lineage to produce an invariant clone of neural progeny. It is critical to identify the genes that specify neuroblast identity as these genes control the time of formation, gene expression profile, and cell lineage characteristics of each neuroblast. Here we show that the Pax-type gooseberry-distal gene specifies row 5 neuroblast identity. Initially, four rows of neuroblasts form per segment (1, 3, 5, 7) and gooseberry-distal is expressed in row 5 neuroblasts. By using 10 molecular markers, and by following the number and orientation of neuroblast divisions, we show that lack of gooseberry-distal transforms row 5 neuroblasts into row 3 neuroblasts, whereas ubiquitous gooseberry-distal generates the reciprocal transformation. Thus, gooseberry-distal is necessary and sufficient to specify row 5 neuroblast identity autonomously. The 10 genes coordinately regulated by gooseberry-distal are prime candidates for controlling specific aspects of neuroblast identity.

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PubMed1995

huckebein specifies aspects of CNS precursor identity required for motoneuron axon pathfinding.

huckebein encodes a putative zinc finger protein expressed in a subset of Drosophila CNS precursors, including the NB 4-2/GMC 4-2a/RP2 cell lineage. In huckebein mutant embryos, GMC 4-2a does not express the cell fate marker EVEN-SKIPPED; conversely, huckebein overexpression produces a duplicate EVEN-SKIPPED-positive GMC 4-2a. We use Dil to trace the entire NB 4-2 lineage in wild-type and huckebein mutant embryos. Loss of huckebein does not affect the number, position, or type of neurons in the NB 4-2 lineage; however, all motoneurons show axon pathfinding defects and never terminate at the correct muscle. Thus, huckebein regulates aspects of GMC and neuronal identity required for proper motoneuron axon pathfinding in the NB 4-2 lineage.

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PubMed1995

The prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila.

Both intrinsic and extrinsic factors are known to regulate sibling cell fate. Here we describe a novel mechanism for the asymmetric localization of a transcription factor to one daughter cell at mitosis. The Drosophila CNS develops from asymmetrically dividing neuroblasts, which give rise to a large neuroblast and a smaller ganglion mother cell (GMC). The prospero gene encodes a transcription factor necessary for proper GMC gene expression. We show that the prospero protein is synthesized in the neuroblast where it is localized to the F-actin cell cortex. At mitosis, prospero is asymmetrically localized to the budding GMC and excluded from the neuroblast. After cytokinesis, prospero is translocated from the GMC cortex into the nucleus. Asymmetric cortical localization of prospero in neuroblasts requires entry into mitosis; it does not depend on numb function. prospero is also observed in cortical crescents in dividing precursors of the peripheral nervous system and adult midgut. The asymmetric cortical localization of prospero at mitosis is a mechanism for rapidly establishing distinct sibling cell fates in the CNS and possibly other tissues.

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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.

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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

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.

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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.

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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.

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