20 results found
Sacchetti P, Sousa KM, Hall AC, et al., 2009, Liver X Receptors and Oxysterols Promote Ventral Midbrain Neurogenesis In Vivo and in Human Embryonic Stem Cells, CELL STEM CELL, Vol: 5, Pages: 409-419, ISSN: 1934-5909
- Author Web Link
- Citations: 100
Bryja V, Andersson ER, Schambony A, et al., 2009, The extracellular domain of Lrp5/6 inhibits noncanonical Wnt signaling in vivo., Mol Biol Cell, Vol: 20, Pages: 924-936
Lrp5/6 are crucial coreceptors for Wnt/beta-catenin signaling, a pathway biochemically distinct from noncanonical Wnt signaling pathways. Here, we examined the possible participation of Lrp5/6 in noncanonical Wnt signaling. We found that Lrp6 physically interacts with Wnt5a, but that this does not lead to phosphorylation of Lrp6 or activation of the Wnt/beta-catenin pathway. Overexpression of Lrp6 blocks activation of the Wnt5a downstream target Rac1, and this effect is dependent on intact Lrp6 extracellular domains. These results suggested that the extracellular domain of Lrp6 inhibits noncanonical Wnt signaling in vitro. In vivo, Lrp6-/- mice exhibited exencephaly and a heart phenotype. Surprisingly, these defects were rescued by deletion of Wnt5a, indicating that the phenotypes resulted from noncanonical Wnt gain-of-function. Similarly, Lrp5 and Lrp6 antisense morpholino-treated Xenopus embryos exhibited convergent extension and heart phenotypes that were rescued by knockdown of noncanonical XWnt5a and XWnt11. Thus, we provide evidence that the extracellular domains of Lrp5/6 behave as physiologically relevant inhibitors of noncanonical Wnt signaling during Xenopus and mouse development in vivo.
Andersson ER, Prakash N, Cajanek L, et al., 2008, Wnt5a regulates ventral midbrain morphogenesis and the development of A9-A10 dopaminergic cells in vivo., PLoS ONE, Vol: 3
Bonilla S, Hall AC, Pinto L, et al., 2008, Identification of midbrain floor plate radial glia-like cells as dopaminergic progenitors., Glia, Vol: 56, Pages: 809-820
The floor plate (FP), a signaling center and a structure rich in radial glia-like cells, has been traditionally thought to be devoid of neurons and neuronal progenitors. However, in the midbrain, the FP contains neurons of the dopaminergic (DA) lineage that require contact with radial glia-like cells for their induction. We, therefore, decided to explore the interaction relationship between radial glia and neurons during DA neurogenesis. Taking advantage of a novel FP radial glia-like cell culture system and retroviruses, DA neurons were lineage traced in vitro. In utero BrdU pulse-chases extensively labeled the midbrain FP and traced DA neurons both in vivo and in FP cultures. Moreover, from E9.5 to E13.5 the midbrain FP contained dividing cells only in the most apical part of the neuroepithelium, in cells identified as radial glia-like cells. We, therefore, hypothesized that midbrain FP radial glia-like cells could be DA progenitors and tested our hypothesis in vivo. Lineage tracing of DA progenitors with EGFP in Tis21-EGFP knock-in mice, and genetic fate mapping in GLAST::CreERT2/ZEG mice identified the neuroepithelium of the midbrain FP, and specifically, GLAST+ radial glia-like cells as DA progenitors. Combined, our experiments support the concept that the midbrain FP differs from other FP regions and demonstrate that FP radial glia-like cells in the midbrain are neurogenic and give rise to midbrain DA neurons.
Sousa KM, Mira H, Hall AC, et al., 2007, Microarray analyses support a role for Nurr1 in resistance to oxidative stress and neuronal differentiation in neural stem cells, STEM CELLS, Vol: 25, Pages: 511-519, ISSN: 1066-5099
- Author Web Link
- Citations: 31
Ahmad-Annuar A, Ciani L, Simeonidis I, et al., 2006, Signaling across the synapse: a role for Wnt and Dishevelled in presynaptic assembly and neurotransmitter release, JOURNAL OF CELL BIOLOGY, Vol: 174, Pages: 127-139, ISSN: 0021-9525
- Author Web Link
- Citations: 177
Prakash N, Brodski C, Naserke T, et al., 2006, A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo, Development, Vol: 133, Pages: 89-98, ISSN: 0950-1991
Bryja V, Cajanek L, Pachernik J, et al., 2005, Abnormal development of mouse embryoid bodies lacking p27Kip1 cell cycle regulator, Stem Cells, Vol: 23, Pages: 965-974, ISSN: 1066-5099
Brunkhorst A, Neuman T, Hall A, et al., 2004, Novel isoforms of the TFIID subunit TAF4 modulate nuclear receptor-mediated transcriptional activity., Biochem Biophys Res Commun, Vol: 325, Pages: 574-579, ISSN: 0006-291X
The transcription factor TFIID consists of TATA-binding protein (TBP) and TBP-associated factors (TAFs). TAFs are essential for modulation of transcriptional activity but the regulation of TAFs is complex and many important aspects remain unclear. In this study, we have identified and characterized five novel truncated forms of the TFIID subunit TAF4 (TAF(II)135). Analysis of the mouse gene structure revealed that all truncations were the results of alternative splicing and resulted in the loss of domains or parts of domains implicated in TAF4 functional interactions. Results from transcriptional assays showed that several of the TAF4 isoforms exerted dominant negative effects on TAF4 activity in nuclear receptor-mediated transcriptional activation. In addition, alternative TAF4 isoforms could be detected in specific cell types. Our results indicate an additional level of complexity in TAF4-mediated regulation of transcription and suggest context-specific roles for these new TAF4 isoforms in transcriptional regulation in vivo.
Hall AC, Mira H, Wagner J, et al., 2003, Region-specific effects of glia on neuronal induction and differentiation with a focus on dopaminergic neurons., Glia, Vol: 43, Pages: 47-51, ISSN: 0894-1491
Radial glia (RG) are the first glial cell type to appear in the nervous system. Their broad distribution and apparent similarity hide important brain region-specific differences that are likely to be essential for development. However, recent evidence supports the stimulating concept that in addition to their classical function as neuroblast guides, RG are neuronal precursors (Malatesta et al. Development 127:5253-5263, 2000; Miyata et al. Neuron 31:727-741, 2001; Noctor et al. Nature 409:714-720, 2001; Skogh et al. Mol Cell Neurosci 17:811-820, 2001). We propose that RG not only generate and guide newborn neurons, but could also instruct their own neuronal progeny to adopt appropriate region-specific phenotypes.
Hall AC, Brennan A, Goold RG, et al., 2002, Valproate regulates GSK-3-mediated axonal remodeling and synapsin I clustering in developing neurons, MOLECULAR AND CELLULAR NEUROSCIENCE, Vol: 20, Pages: 257-270, ISSN: 1044-7431
- Author Web Link
- Citations: 146
Tekki-Kessaris N, Woodruff R, Hall AC, et al., 2001, Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon., Development, Vol: 128, Pages: 2545-2554, ISSN: 0950-1991
In the caudal neural tube, oligodendrocyte progenitors (OLPs) originate in the ventral neuroepithelium under the influence of Sonic hedgehog (SHH), then migrate throughout the spinal cord and brainstem before differentiating into myelin-forming cells. We present evidence that oligodendrogenesis in the anterior neural tube follows a similar pattern. We show that OLPs in the embryonic mouse forebrain express platelet-derived growth factor alpha-receptors (PDGFRA), as they do in more caudal regions. They first appear within a region of anterior hypothalamic neuroepithelium that co-expresses mRNA encoding SHH, its receptor PTC1 (PTCH) and the transcription factors OLIG1, OLIG2 and SOX10. Pdgfra-positive progenitors later spread through the forebrain into areas where Shh is not expressed, including the cerebral cortex. Cyclopamine inhibited OLP development in cultures of mouse basal forebrain, suggesting that hedgehog (HH) signalling is obligatory for oligodendrogenesis in the ventral telencephalon. Moreover, Pdgfra-positive progenitors did not appear on schedule in the ventral forebrains of Nkx2.1 null mice, which lack the telencephalic domain of Shh expression. However, OLPs did develop in cultures of Nkx2.1(-/-) basal forebrain and this was blocked by cyclopamine. OLPs also developed in neocortical cultures, even though Shh transcripts could not be detected in the embryonic cortex. Here, too, the appearance of OLPs was suppressed by cyclopamine. In keeping with these findings, we detected mRNA encoding SHH and Indian hedgehog (IHH) in both Nkx2.1(-/-) basal forebrain cultures and neocortical cultures. Overall, the data are consistent with the idea that OLPs in the telencephalon, possibly even some of those in the cortex, develop under the influence of SHH in the ventral forebrain.
Richardson WD, Smith HK, Sun T, et al., 2000, Oligodendrocyte lineage and the motor neuron connection., Glia, Vol: 29, Pages: 136-142, ISSN: 0894-1491
One of the more surprising recent discoveries in glial biology has been that oligodendrocytes (OLs) originate from very restricted regions of the embryonic neural tube. This was surprising because myelinating OLs are widespread in the mature central nervous system, so there was no reason to suspect that their precursors should be restricted. What we now know about early OL development suggests that they might have as much (or more) in common with ventral neurons-specifically motor neurons (MNs)-as with other types of glia. This has implications for the way we think about glial development, function, and evolution. In this article we review the evidence for a shared MN-OL lineage and debate whether this is the only lineage that generates OLs. We decide in favour of a single embryonic lineage with regional variations along the anterior-posterior neuraxis.
Hall AC, Lucas FR, Salinas PC, 2000, Axonal remodelling and synaptic differentiation in the cerebellum is regulated by Wnt7a signalling, Cell, Vol: 100, Pages: 525-535
Fruttiger M, Karlsson L, Hall AC, et al., 1999, Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice., Development, Vol: 126, Pages: 457-467, ISSN: 0950-1991
There is a class of oligodendrocyte progenitors, called O-2A progenitors, that is characterized by expression of platelet-derived growth factor &agr;-receptors (PDGFR(&agr;)). It is not known whether all oligodendrocytes are derived from these PDGFRalpha-progenitors or whether a subset(s) of oligodendrocytes develops from a different, PDGFR alpha-negative lineage(s). We investigated the relationship between PDGF and oligodendrogenesis by examining mice that lack either PDGF-A or PDGF-B. PDGF-A null mice had many fewer PDGFR alpha-progenitors than either wild-type or PDGF-B null mice, demonstrating that proliferation of these cells relies heavily (though not exclusively) on PDGF-AA homodimers. PDGF-A-deficient mice also had reduced numbers of oligodendrocytes and a dysmyelinating phenotype (tremor). Not all parts of the central nervous system (CNS) were equally affected in the knockout. For example, there were profound reductions in the numbers of PDGFR alpha-progenitors and oligodendrocytes in the spinal cord and cerebellum, but less severe reductions of both cell types in the medulla. This correlation suggests a close link between PDGFRalpha-progenitors and oligodendrogenesis in most or all parts of the CNS. We also provide evidence that myelin proteolipid protein (PLP/DM-20)-positive cells in the late embryonic brainstem are non-dividing cells, presumably immature oligodendrocytes, and not proliferating precursors.
Salinas PC, Hall AC, 1999, Lithium and synaptic plasticity, Bipolar disorders, Vol: 2, Pages: 87-90
Calver AR, Hall AC, Yu WP, et al., 1998, Oligodendrocyte population dynamics and the role of PDGF in vivo., Neuron, Vol: 20, Pages: 869-882, ISSN: 0896-6273
Oligodendrocyte progenitors originate near the floor plate of the spinal cord, then proliferate and migrate throughout the cord before giving rise to oligodendrocytes. Progenitor cell proliferation stops before birth because the cell cycle slows down, linked to an increase in differentiation and death. Experiments with transgenic mice show that platelet-derived growth factor (PDGF) drives progenitor cell division and suggest that slowing of and exit from the cycle reflects a decline in PDGF signaling. Overexpressing PDGF induces hyperproliferation of progenitor cells and excessive, ectopic production of oligodendrocytes. However, the superfluous oligodendrocytes die at an immature stage of differentiation, leaving a normal complement of myelin-forming cells. Therefore, cell survival controls override proliferation controls for determining the final number and distribution of mature oligodendrocytes.
Richardson WD, Pringle NP, Yu WP, et al., 1997, Origins of spinal cord oligodendrocytes: possible developmental and evolutionary relationships with motor neurons., Dev Neurosci, Vol: 19, Pages: 58-68, ISSN: 0378-5866
Spinal cord oligodendrocytes develop from migratory glial progenitor cells that are generated by a small subset of neuroepithelial cells in the ventral part of the neural tube. Specification of these neuroepithelial oligodendrocyte precursors, in common with other ventral cells such as motor neurons, depends on morphogenetic signals from the notochord and/or floor plate. The ventrally derived signals can be mimicked in vitro by purified Sonic hedgehog (Shh) protein. Oligodendrocytes and motor neurons are induced over the same range of concentrations of Shh, consistent with the idea that Shh might specify a common precursor of motor neurons and oligodendrocytes. A lineage relationship between motor neurons and oligodendrocytes has previously been suggested by clonal analysis in the embryonic chick spinal cord. We propose a lineage diagram that connects oligodendrocytes and motor neurons and that takes into account the fact that motor neurons and oligodendrocyte precursors are generated at different times during development. Oligodendrocytes might originally have evolved to ensheath motor axons and facilitate a rapid escape response. If so, oligodendrocyte ontogeny and phylogeny might share a common basis.
Hall A, Giese NA, Richardson WD, 1996, Spinal cord oligodendrocytes develop from ventrally derived progenitor cells that express PDGF alpha-receptors., Development, Vol: 122, Pages: 4085-4094, ISSN: 0950-1991
Platelet-derived growth factor alpha-receptors (PDGFR alpha) are expressed by a subset of neuroepithelial cells in the ventral half of the embryonic day 14 (E14) rat spinal cord. The progeny of these cells subsequently proliferate and migrate into the dorsal parts of the cord after E16. Here, we show that E14 ventral cells are able to generate oligodendrocytes in culture but that dorsal cells acquire this ability only after E16, coinciding with the appearance of PDGFR alpha-immunoreactive cells in the starting population. PDGFR alpha-positive cells in optic nerve and spinal cord cultures co-labelled with antibody markers of oligodendrocyte progenitors. When PDGFR alpha-positive cells were purified from embryonic rat spinal cords by immunoselection and cultured in defined medium, they all differentiated into oligodendrocytes. Very few oligodendrocytes developed in cultures of embryonic spinal cord cells that had been depleted of PDGFR alpha-expressing cells by antibody-mediated complement lysis. These data demonstrate that all PDGFR alpha-positive cells in the embryonic rat spinal cord are oligodendrocyte progenitors and that most or all early-developing oligodendrocytes are derived from these ventrally-derived precursors.
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