Directed differentiation of neural cells to hypothalamic dopaminergic neurons

Ohyama, Katsumi; Ellis, Pamela; Kimura, Shioko; Placzek, Marysia

doi:10.1242/dev.02094

Cited by 88 publications

(104 citation statements)

References 46 publications

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“…Antibodies used were against Pax6, Pax7, Pax2, Evx1, Nkx2.2, Isl1, Lim1/Lim2, Lmx1b, N-cadherin, Nkx6.1 and En1 (DSHB); mouse anti--catenin (Sigma); rabbit anti-Dbx1 (Pierani et al, 1999); anti-Chx10 (S. Morton, Columbia University, NY, USA); rabbit anti-Pax6 (Covance); rabbit anti-Olig2 polyclonal and rabbit anti-RFP polyclonal (Chemicon); rabbit anti-phospho-histone H3 polyclonal (Upstate); rabbit anti-GFP polyclonal (BD Bioscience); anti-Crb2 (P. Rashbass, University of Sheffield, UK); rabbit anti-pYap1 polyclonal (Cell Signaling Technology); and Alexa405-, Alexa488-and Alexa555-conjugated secondary antibodies were obtained from Molecular Probes (Invitrogen). Whole-mount in situ hybridisation was performed as previously described (Ohyama et al, 2005;Das et al, 2006) using digoxigenin (DIG)-labelled (Roche) RNA probes. DIG-labelled antisense riboprobes were generated from chicken EST plasmids ChEST187n19 (FatJ); ChEST427d5 (Yap1) and ChEST580f24 (Tead4) [by linearization with NotI and transcription with T3 RNA polymerase (Promega)].…”

Section: Embryo Fixation Immunohistochemistry and In Situ Hybridisationmentioning

confidence: 99%

FatJ acts via the Hippo mediator Yap1 to restrict the size of neural progenitor cell pools

et al. 2011

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SUMMARYThe size, composition and functioning of the spinal cord is likely to depend on appropriate numbers of progenitor and differentiated cells of a particular class, but little is known about how cell numbers are controlled in specific cell cohorts along the dorsoventral axis of the neural tube. Here, we show that FatJ cadherin, identified in a large-scale RNA interference (RNAi) screen of cadherin genes expressed in the neural tube, is localised to progenitors in intermediate regions of the neural tube. Loss of function of FatJ promotes an increase in dp4-vp1 progenitors and a concomitant increase in differentiated Lim1 + /Lim2 + neurons. Our studies reveal that FatJ mediates its action via the Hippo pathway mediator Yap1: loss of downstream Hippo components can rescue the defect caused by loss of FatJ. Together, our data demonstrate that RNAi screens are feasible in the chick embryonic neural tube, and show that FatJ acts through the Hippo pathway to regulate cell numbers in specific subsets of neural progenitor pools and their differentiated progeny.

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Section: Embryo Fixation Immunohistochemistry and In Situ Hybridisationmentioning

confidence: 99%

FatJ acts via the Hippo mediator Yap1 to restrict the size of neural progenitor cell pools

et al. 2011

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“…Chick embryos (n=5-10; each stage) and explants (n=5-20) were examined as described previously (Ohyama et al, 2005). Antibodies used were: 5E1 anti-Shh mAb (1:50); anti-Pax7 mAb (1:50); anti-Lim1 (4F8); anti-Msx1/2 (4G1: 1:50) (all from DSHB); Kyo2-60 anti-Nkx2.1 polyclonal antibody (1:2000); anti-Gsh polyclonal antibody (1:2000); NCL-Ki67-PKi67 antihuman (Novocastra, 1:3000); anti-Isl1 polyclonal antibody (1:800); AB3216 anti-RFP polyclonal antibody (Chemicon, 1:1000); anti-GFP polyclonal (BD 632576, 1:1000); anti-pSmad1/5/8 (Cell Signaling 95115, 1:100-1:500).…”

Section: Immunolabellingmentioning

confidence: 99%

“…In contrast to other regions of the neural tube, in the hypothalamus, Shh and BMPs are expressed in a spatially overlapping, but temporally consecutive manner (Dale et al, 1997;Dale et al, 1999;Ohyama et al, 2005;Manning et al, 2006). Here, we examine the mechanism by which this discrete signalling profile governs downstream Gli effectors and hypothalamic transcriptional signatures.…”

Section: Introductionmentioning

confidence: 99%

Temporal progression of hypothalamic patterning by a dual action of BMP

2008

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In the developing chick hypothalamus, Shh and BMPs are expressed in a spatially overlapping, but temporally consecutive, manner. Here, we demonstrate how the temporal integration of Shh and BMP signalling leads to the late acquisition of Pax7 expression in hypothalamic progenitor cells. Our studies reveal a requirement for a dual action of BMPs: first, the inhibition of GliA function through Gli3 upregulation; and second, activation of a Smad5-dependent BMP pathway. Previous studies have shown a requirement for spatial antagonism of Shh and BMPs in early CNS patterning; here, we propose that neural pattern elaboration can be achieved through a versatile temporal antagonism between Shh and BMPs.

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“…Although transcriptional input from local prepattern would suggest that multiple transcriptional modules might converge on specification of the DA neurotransmitter phenotype (Ohyama et al, 2005;Smidt and Burbach, 2007;Löhr et al, 2009), our observations on dla/dld in zebrafish and previous reports on Dll1 in mammals (Kele et al, 2006) suggest a unifying mechanism for DA neurogenesis. This mechanism appears to apply both to DA systems established by primary neurogenesis from neural plate cells as well as to neural stem and precursor cell-based mechanisms that control continuous expansion of later developing DA systems.…”

Section: Discussionmentioning

confidence: 41%

DeltaA/DeltaD Regulate Multiple and Temporally Distinct Phases of Notch Signaling during Dopaminergic Neurogenesis in Zebrafish

Mahler¹,

Filippi²,

Driever³

2010

J. Neurosci.

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Dopaminergic neurons develop at distinct anatomical sites to form some of the major neuromodulatory systems in the vertebrate brain. Despite their relevance in neurodegenerative diseases and the interests in reconstitutive therapies from stem cells, mechanisms of the neurogenic switch from precursor populations to dopaminergic neurons are not well understood. Here, we investigated neurogenesis of different dopaminergic and noradrenergic neuron populations in the zebrafish embryo. Birth-dating analysis by EdU (5-ethynyl-2Ј-deoxyuridine) incorporation revealed temporal dynamics of catecholaminergic neurogenesis. Analysis of Notch signaling mutants and stage-specific pharmacological inhibition of Notch processing revealed that dopaminergic neurons form by temporally distinct mechanisms: dopaminergic neurons of the posterior tuberculum derive directly from neural plate cells during primary neurogenesis, whereas other dopaminergic groups form in continuous or wavelike neurogenesis phases from proliferating precursor pools. Systematic analysis of Notch ligands revealed that the two zebrafish co-orthologs of mammalian Delta1, DeltaA and DeltaD, control the neurogenic switch of all early developing dopaminergic neurons in a partially redundant manner. DeltaA/D may also be involved in maintenance of dopaminergic precursor pools, as olig2 expression in ventral diencephalic dopaminergic precursors is affected in dla/dld mutants. DeltaA/D act upstream of sim1a and otpa during dopaminergic specification. However, despite the fact that both dopaminergic and corticotropinreleasing hormone neurons derive from sim1a-and otpa-expressing precursors, DeltaA/D does not act as a lineage switch between these two neuronal types. Rather, DeltaA/D limits the size of the sim1a-and otpa-expressing precursor pool from which dopaminergic neurons differentiate.

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Directed differentiation of neural cells to hypothalamic dopaminergic neurons

Cited by 88 publications

References 46 publications

FatJ acts via the Hippo mediator Yap1 to restrict the size of neural progenitor cell pools

FatJ acts via the Hippo mediator Yap1 to restrict the size of neural progenitor cell pools

Temporal progression of hypothalamic patterning by a dual action of BMP

DeltaA/DeltaD Regulate Multiple and Temporally Distinct Phases of Notch Signaling during Dopaminergic Neurogenesis in Zebrafish

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