Ectopic Pax2 expression in chick ventral optic cup phenocopies loss of Pax2 expression.

Pax2 is essential for the development of the urogenital system, neural tube, otic vesicle, optic cup and optic tract [Dressler, G.R., Deutsch, U., et al., 1990. PAX2, a new murine paired-box-containing gene and its expression in the developing excretory system. Development 109 (4), 787-795; Nornes, H.O., Dressler, G.R., et al., 1990. Spatially and temporally restricted expression of Pax2 during murine neurogenesis. Development 109 (4), 797-809; Eccles, M.R., Wallis, L.J., et al., 1992. Expression of the PAX2 gene in human fetal kidney and Wilms' tumor. Cell Growth Differ 3 (5), 279-289]. Within the visual system, a loss-of-function leads to lack of choroid fissure closure (known as a coloboma), a loss of optic nerve astrocytes, and anomalous axonal pathfinding at the optic chiasm [Favor, J., Sandulache, R., et al., 1996. The mouse Pax2(1Neu) mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye, and kidney. Proc. Natl. Acad. Sci. U. S. A. 93 (24), 13870-13875; Torres, M., Gomez-Pardo, E., et al., 1996. Pax2 contributes to inner ear patterning and optic nerve trajectory. Development 122 (11), 3381-3391]. This study is directed at determining the effects of ectopic Pax2 expression in the chick ventral optic cup past the normal developmental period when Pax2 is found. In ovo electroporation of Pax2 into the chick ventral optic cup results in the formation of colobomas, a condition typically associated with a loss of Pax2 expression. While the overexpression of Pax2 appears to phenocopy a loss of Pax2, the mechanism of the failure of choroid fissure closure is associated with a cell fate switch from ventral retina and retinal pigmented epithelium (RPE) to an astrocyte fate. Further, ectopic expression of Pax2 in RPE appears to have non-cell autonomous effects on adjacent RPE, creating an ectopic neural retina in place of the RPE.

Generating neuronal diversity in the Drosophila central nervous system: a view from the ganglion mother cells.

The generation of cellular diversity in the developing embryonic central nervous system of Drosophila melanogaster requires the precise orchestration of several convergent molecular and cellular mechanisms. Most reviews have focused on the formation and specification of neuroblasts (NBs), the putative neural stem cell in the Drosophila central nervous system. NBs divide asymmetrically to regenerate themselves and produce a secondary precursor cell called a ganglion mother cell (GMC), which divides to produce neurons and glia. Historically, our understanding of GMC specification has arisen from work involving asymmetric localization of intrinsic factors in the NB and GMC. However, recent information on NB lineages has revealed additional intrinsic factors that specify general and specific GMC fates. This review addresses what has been revealed about these intrinsic cues with regard to GMC specification. For example, Prospero, an asymmetrically localized determinant, plays a general role to enable GMC development and to distinguish GMCs from NBs. In contrast, the temporal gene cascade functions within NB lineages to ensure that each GMC in a lineage acquires a different fate. Two different mechanisms used to make the progeny of GMCs different will also be discussed. One is a generic mechanism, regulated by Notch and Numb, that allows sibling cells to adopt different fates. The other mechanism involves genes, such as even-skipped and klumpfuss that specify the fate of individual GMCs. All of these mechanisms converge within a GMC to bestow upon it a unique fate.

Drosophila neuroblast 7-3 cell lineage: a model system for studying programmed cell death, Notch/Numb signaling, and sequential specification of ganglion mother cell identity.

Cell lineage studies provide an important foundation for experimental analysis in many systems. Drosophila neural precursors (neuroblasts) sequentially generate ganglion mother cells (GMCs), which generate neurons and/or glia, but the birth order, or cell lineage, of each neuroblast is poorly understood. The best-characterized neuroblast is NB7-3, in which GMC-1 makes the EW1 serotonergic interneuron and GW motoneuron; GMC-2 makes the EW2 serotonergic interneuron and a programmed cell death; and GMC-3 gives rise to the EW3 interneuron. However, the end of this lineage has not been determined. Here, we use positively marked genetic clones, bromodeoxyuridine (BrdU) labeling, mutations that affect Notch signaling, and antibody markers to further define the end of the cell lineage of NB7-3. We provide evidence that GMC-3 directly differentiates into EW3 and that the sibling neuroblast undergoes programmed cell death. Our results confirm and extend previous work on the early portion of the NB7-3 lineage (Novotny et al. [2002] Development 129:1027-1036; Lundell et al. [ 2003] Development 130:4109-4121).

Spinal cord regeneration: intrinsic properties and emerging mechanisms.

Injured spinal cord regenerates in adult fish and urodele amphibians, young tadpoles of anuran amphibians, lizard tails, embryonic birds and mammals, and in adults of at least some strains of mice. The extent of this regeneration is described with respect to axonal regrowth, neurogenesis, glial responses, and maintenance of an 'embryonic' environment. The regeneration process in amphibian spinal cord demonstrates that gap replacement and caudal regeneration share some properties with developing spinal cord. This review considers the extent to which intrinsically regenerating spinal cord demonstrates neural stem cell behavior and to what extent anterior-posterior and dorsal-ventral patterning might be involved.