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C Q Doe

Publications and source records attributed to C Q Doe.

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From epithelium to neuroblasts to neurons: the role of cell interactions and cell lineage during insect neurogenesis.

The grasshopper central nervous system is composed of a brain and a chain of segmental ganglia. Each hemiganglion contains about 1000 neurons, most of which can be individually identified by their unique morphology and synaptic connectivity. Shortly after gastrulation the ventral ectoderm becomes a neurogenic region. In each hemisegment, ca. 150 neurogenic ectodermal cells (nECs) give rise to a stereotyped pattern of 30 identified neuroblasts (NBs, neuronal stem cells); the remaining nECs become various non-neuronal cells or die. The 30 NBs then give rise to about 1000 neurons as each NB initiates an invariant lineage, generating a stereotyped chain of ganglion mother cells (GMCs), each of which in turn divides once to generate two identified neurons. We have used a laser microbeam or microelectrode to ablate individual cells in ovo and in vitro at various stages of embryogenesis to study how neuronal diversity and specificity are generated during development. Our results suggest that cell interactions between ca. 150 equivalent nECs allow 30 cells to enlarge into NBs, the dominant fate in a hierarchy; the NBs inhibit adjacent nECs and thus cause them to differentiate into various non-neuronal cells; each NB is assigned its unique identity according to its position of enlargement within the neurogenic epithelium; each NB then generates its characteristic chain of GMCs by an invariant cell lineage; and each GMC generates a pair of equivalent progeny, the fate of each individual neuron being determined by both its GMC of origin and interactions with its sibling.

Cell Communication↗

Early events in insect neurogenesis. I. Development and segmental differences in the pattern of neuronal precursor cells.

The earliest events in the development of the central nervous system in insect embryos involve the differentiation of a stereotyped pattern of individually identified neuronal precursor cells, called neuroblasts (NBs), each of which generates a stereotyped family of neuronal progeny. After gastrulation, the midventral region of the ectoderm becomes a neuroepithelium; it is from this sheet of seemingly uniform ectodermal cells that certain cells enlarge to become NBs while the rest of the cells either die or acquire other nonneuronal phenotypes. Here we focus on three aspects of neurogenesis. First, we examine the morphological changes associated with the differentiation of neuronal precursor cells and nonneuronal support cells. The differentiation of each cell type is reflected by its morphology; moreover, the identity of individual cells of certain cell types (e.g., a particular NB) is reflected by their position within the neuroepithelium. Second, we show that there is a characteristic temporal sequence of differentiation in the stereotyped pattern of NBs. Third, we show that this stereotyped pattern of NBs varies in a segment-specific way by the addition or deletion of particular neuronal precursor cells. These studies on the events of early neurogenesis set the stage for the experimental manipulations described in the following paper (C. Q. Doe and C.S. Goodman, 1985, Dev. Biol. 110, 206-219).

Abdomen↗

Early events in insect neurogenesis. II. The role of cell interactions and cell lineage in the determination of neuronal precursor cells.

The insect central nervous system (CNS) is composed of a brain and a chain of segmental ganglia; each hemiganglion contains about 1000 individually identifiable neurons. How is the enormous neuronal diversity and specificity generated? Neurons of a hemiganglion largely arise during embryogenesis from a stereotyped pattern of individually identified neuronal precursor cells, called neuroblasts (NBs). The transition from ectoderm to individual neurons thus involves two major steps: first, an undifferentiated ectodermal cell sheet produces the stereotyped pattern of 30 NBs per hemisegment; second, each of these NBs contributes a specific family of neuronal progeny to the developing CNS. We have used a laser microbeam to ablate individual cells in the grasshopper embryo in order to study the initial events of neuronal determination. In particular, how does a layer of apparently equivalent ectodermal cells produce a highly stereotyped pattern of unique NBs? Our results suggest the following mechanism for NB determination. (1) Cell interactions between the approximately 150 equivalent ectodermal cells of a hemisegment allow 30 cells to enlarge into NBs. (2) As these young NBs enlarge they inhibit adjacent ectodermal cells from becoming NBs; the adjacent cells then either differentiate into nonneuronal support cells or die. (3) Each NB is assigned a unique identity due to its position of enlargement within the neuroepithelium. (4) The NB then generates its characteristic family of neurons by an invariant cell lineage. Development of the insect CNS depends on cell interactions and positional cues to create a pattern of NBs, and then on cell lineage to restrict the fate of the NB progeny.

Animals↗

Cell recognition during neuronal development.

Insect embryos, with their relatively simple nervous systems, provide a model system with which to study the cellular and molecular mechanisms underlying cell recognition during neuronal development. Such an approach can take advantage of the accessible cells of the grasshopper embryo and the accessible genes of Drosophila. The growth cones of identified neurons express selective affinities for specific axonal surfaces; such specificities give rise to the stereotyped patterns of selective fasciculation common to both species. These and other results suggest that early in development cell lineage and cell interactions lead to the differential expression of cell recognition molecules on the surfaces of small subsets of embryonic neurons whose axons selectively fasciculate with one another. Monoclonal antibodies reveal surface molecules in the Drosophila embryo whose expression correlates with this prediction. It should now be possible to isolate the genes encoding these potential cell recognition molecules and to test their function through the use of molecular genetic approaches in Drosophila.

Animals↗

Cell determination and regulation during development of neuroblasts and neurones in grasshopper embryo.

The embryonic development of the central nervous system (CNS) involves the generation of an enormous diversity of cellular types arranged and interconnected in a remarkably precise pattern. In each hemisegment of the grasshopper embryo, the ectoderm generates a stereotyped pattern of 30 neuronal precursor cells, called neuroblasts (Fig. 1). Each of these stem cells makes a stereotyped contribution of 6-100 progeny to the approximately 1,000 different neurones, each cell identifiable according to its unique morphology, physiology and biochemistry. What are the contributions of cell interactions and cell lineage to the generation of this diversity and specificity of identified neurones in the grasshopper CNS? Here we report on cell ablations with a laser microbeam at different stages of development. Our results suggest the importance of cell-cell interactions in the determination of ectodermal cells to become identified neuroblasts. However, once a neuroblast begins to divide, then cell lineage appears to play an important role in the determination of its stereotyped family of neuronal progeny. Furthermore, cell-specific interactions continue to play an important role as neurones, according to their mitotic ancestry, recognize and interact with other differentiating neurones in their environment.

Animals↗