Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain

Price, Melanie; Lazzaro, Domenico; Pohl, Thomas; Matteï, Marie‐Geneviève; Rüther, Ulrich; Olivo, Jean-Christophe; Duboule, Denis; Lauro, Roberto Di

doi:10.1016/0896-6273(92)90291-k

Cited by 282 publications

(173 citation statements)

References 26 publications

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“…In situ hybridization on frozen sections of paraformaldehyde-fixed tissues with digoxigeninlabeled antisense probes was performed essentially as described in Ma et al (1997), and photomicrographs were collected on a Nikon E600 compound microscope using a SPOT I digital camera (Diagnostic Imaging). We thank the following investigators for kindly supplying the in situ hybridization probes used: M. Scott (P tc-1) ; A. Joyner (Gli-1) (Hui et al, 1994); B. Hogan (HNF3␤) (Sasaki and Hogan, 1993); P. Gruss (Pax-6 ) (Walther and Gruss, 1991) (Pax-3) (Goulding et al, 1993); J. Rubinstein (Nk x -2.2) (Price et al, 1992); R. Johnson (Lmx -1b) (Chen et al, 1998); D. Lachman (Brn-3a) (Theil et al, 1994); L. Roberston (BMP-7 ) (Lyons et al, 1995); R. Kageyama (HES-1) (Sasai et al, 1992); Genetics Institute, C ambridge, M A (GDF-7 ) (Storm et al, 1994).…”

Section: Methodsmentioning

confidence: 99%

Sonic hedgehogRegulates Proliferation and Inhibits Differentiation of CNS Precursor Cells

et al. 1999

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Activation of the Sonic hedgehog (Shh) signal transduction pathway is essential for normal pattern formation and cellular differentiation in the developing CNS. However, it is also thought to be etiological in primitive neuroectodermal tumors. We adapted GAL4/UAS methodology to ectopically express full-length Shh in the dorsal neural tube of transgenic mouse embryos commencing at 10 d postcoitum (dpc), beyond the period of primary dorsal-ventral pattern formation and floorplate induction. Expression of Shh was maintained until birth, permitting us to investigate effects of ongoing exposure to Shh on CNS precursors in vivo. Proliferative rates of spinal cord precursors were twice that of wild-type littermates at 12.5 dpc. In contrast, at late fetal stages (18.5 dpc), cells that were Shh-responsive but postmitotic were present in persistent structures reminiscent of the ventricular zone germinal matrix. This tissue remained blocked in an undifferentiated state. These results indicate that cellular competence restricts the proliferative response to Shh in vivo and provide evidence that proliferation and differentiation can be regulated separately in precursor cells of the spinal cord. Thus, Hedgehog signaling may contribute to CNS tumorigenesis by directly enhancing proliferation and preventing neural differentiation in selected precursor cells.

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Section: Methodsmentioning

confidence: 99%

Sonic hedgehogRegulates Proliferation and Inhibits Differentiation of CNS Precursor Cells

et al. 1999

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“…6C,D). Expression of Nkx2-1, an essential marker of the early hypothalamus as a region, is restricted during differentiation to specific hypothalamic nuclei including part of the preoptic area and the mamillary body (Price et al, 1992) (Fig. 6 E).…”

Section: The Ventral Diencephalon Of the Shh-c Is Transversally Dividmentioning

confidence: 99%

Role of NeuroepithelialSonic hedgehogin Hypothalamic Patterning

et al. 2009

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The hypothalamus is a region of the diencephalon with particularly complex patterning. Sonic hedgehog (Shh), encoding a protein with key developmental roles, shows a peculiar and dynamic diencephalic expression pattern. Here, we use transgenic strategies and in vitro experiments to test the hypothesis that Shh expressed in the diencephalic neuroepithelium (neural Shh) coordinates tissue growth and patterning in the hypothalamus. Our results show that neural Shh coordinates anteroposterior and dorsoventral patterning in the hypothalamus and in the diencephalon-telencephalon junction. Neural Shh also coordinates mediolateral hypothalamic patterning, since it is necessary for the lateral hypothalamus to attain proper size and is required for the specification of hypocretin/orexin cells. Finally, neural Shh is necessary to maintain expression of differentiation markers including survival factor Foxb1.

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“…Within the Drosophila neuroectoderm, the ventral column is specified by vnd function (this paper; Skeath et al 1994), the intermediate column is specified by ind function , and the dorsal column appears to be partially or completely specified by msh function (Isshiki et al 1997). Interestingly, the closest vertebrate homologs to each of these three genes is expressed in analogous DV domains during neurogenesis: The mouse Nkx2.1, Nkx2.2, and Nkx2.9 genes are vnd homologs expressed in ventral neuroectoderm domains adjacent to the floor plate (Guazzi et al 1990;Price et al 1992;Pabst et al 1998); the mouse Gsh-1 and Gsh-2 genes are ind homologs expressed in intermediate neuroectodermal domains (Hsieh-Li et al 1995;Valerius et al 1995); and the mouse Msx genes are homologs of msh expressed in dorsal neuroectodermal domains (for review, see Davidson 1995). To determine whether the Nkx, Gsh, and Msx homeobox genes control DV patterning of the vertebrate CNS, similar to the function of the Drosophila vnd, ind, and msh genes, may require the generation of double or triple knockouts to overcome possible functional redundancy among the closely related genes within each family.…”

Section: Parallels With Vertebrate Neural Patterningmentioning

confidence: 99%

Dorsoventral patterning in the Drosophila central nervous system: the vnd homeobox gene specifies ventral column identity

McDonald¹,

Holbrook²,

Isshiki³

et al. 1998

Genes Dev.

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The Drosophila embryonic central nervous system (CNS) develops from a bilateral neuroectoderm that forms adjacent to the specialized cells of the ventral midline. Neuroectoderm on each side of the ventral midline can be subdivided, on the basis of patterns of gene expression and neuroblast formation, into an orthogonal grid of four rows (1, 3, 5, 7) along the anteroposterior (AP) axis and three columns (ventral, intermediate, and dorsal) along the DV axis. The earliest neuroblast array has four neuroblasts in the ventral column, two in the intermediate column, and four in the dorsal column. Neuroblasts divide repeatedly to produce a series of smaller ganglion mother cells (GMCs), each of which produce two postmitotic neurons or glia. Every neuroblast is uniquely identifiable on the basis of its AP and DV position, and each generates a characteristic family of neurons and glia.Neuroblast formation is regulated by the proneural genes achaete, scute, and lethal of scute (for review, see Campos-Ortega 1993). Each of these proneural genes is expressed in clusters of 4-6 cells at different positions within the neuroectoderm (e.g., achaete is expressed in four clusters, in the ventral and dorsal columns of rows 3 and 7). Proneural genes promote the formation of neuroblasts, whereas Delta-Notch signaling inhibits neuroblast formation; the balance of proneural and Notch activity results in the formation of a single neuroblast from each cluster (for review, see Campos-Ortega 1993).What are the cues that specify correct neuroblast identity along the AP and DV axes? The segment polarity genes wingless, hedgehog, gooseberry, and engrailed are expressed in stripes in the neuroectoderm and specify the AP row identity of neuroblasts (Chu-LaGraff and Doe 1993;Zhang et al. 1994;Skeath et al. 1995;Bhat 1996;Matsuzaki and Saigo 1996;Bhat and Schedl 1997). Conditional inactivation (for wingless; Chu-LaGraff and Doe 1993) or misexpression (for gooseberry; Skeath et al. 1995) experiments show that segment polarity gene function is required in the neuroectoderm, prior to neuroblast delamination, for the proper specification of neuroblast identity.Less is known about how neuroectoderm and neuro-

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Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain

Cited by 282 publications

References 26 publications

Sonic hedgehogRegulates Proliferation and Inhibits Differentiation of CNS Precursor Cells

Sonic hedgehogRegulates Proliferation and Inhibits Differentiation of CNS Precursor Cells

Role of NeuroepithelialSonic hedgehogin Hypothalamic Patterning

Dorsoventral patterning in the Drosophila central nervous system: the vnd homeobox gene specifies ventral column identity

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