A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord

Borromeo, Mark D.; Meredith, David M.; Castro, Diogo S.; Chang, Joshua C.; Tung, Kuang-Chi; Guillemot, François; Johnson, Jane E.

doi:10.1242/dev.114728

Cited by 21 publications

(29 citation statements)

References 28 publications

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“…To determine whether Pax6 binds this enhancer, ChIP-qPCR was performed on caudal neural tube tissues from E11.5 embryos using an anti-Pax6 antibody (Coutinho et al, 2011) and primers that span the identified potential Pax6 binding sites. This region was found to be significantly enriched compared with a negative control region (Kirrel2) (Borromeo et al, 2014) (supplementary material Fig. S8).…”

Section: Cloning and Expression Of Xenopus Chicken And Amphioxus Prdmentioning

confidence: 99%

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Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus

et al. 2015

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V1 interneurons are inhibitory neurons that play an essential role in vertebrate locomotion. The molecular mechanisms underlying their genesis remain, however, largely undefined. Here, we show that the transcription factor Prdm12 is selectively expressed in p1 progenitors of the hindbrain and spinal cord in the frog embryo, and that a similar restricted expression profile is observed in the nerve cord of other vertebrates as well as of the cephalochordate amphioxus. Using frog, chick and mice, we analyzed the regulation of Prdm12 and found that its expression in the caudal neural tube is dependent on retinoic acid and Pax6, and that it is restricted to p1 progenitors, due to the repressive action of Dbx1 and Nkx6-1/2 expressed in the adjacent p0 and p2 domains. Functional studies in the frog, including genomewide identification of its targets by RNA-seq and ChIP-Seq, reveal that vertebrate Prdm12 proteins act as a general determinant of V1 cell fate, at least in part, by directly repressing Dbx1 and Nkx6 genes. This probably occurs by recruiting the methyltransferase G9a, an activity that is not displayed by the amphioxus Prdm12 protein. Together, these findings indicate that Prdm12 promotes V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes, and suggest that this function might have only been acquired after the split of the vertebrate and cephalochordate lineages.

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Section: Cloning and Expression Of Xenopus Chicken And Amphioxus Prdmentioning

confidence: 99%

“…ChIP was essentially conducted in mouse (Borromeo et al, 2014) and in Xenopus as described (Ma et al, 2014;Colin et al, 2011) (see supplementary material methods). RNAseq and ChIP data have been deposited at GEO under accession GSE64551.…”

Section: Rna Sequencing and Chromatin Immunoprecipitationmentioning

confidence: 99%

Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus

et al. 2015

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“…Furthermore, WM OPCs can proliferate in response to the growth factor PDGF but GM OPCs cannot (Hill et al, 2013). Given that the function of Ascl1 in the CNS is highly dynamic and context dependent (Helms et al, 2005;Mizuguchi et al, 2006;Wildner et al, 2006;Jacob et al, 2013), and that Ascl1 has been shown to regulate a complex set of downstream targets Borromeo et al, 2014), it is possible that Ascl1 in the oligodendrocyte lineages directly contributes to the differences in their intrinsic properties in the GM and WM.…”

Section: Ascl1 Is Required To Balance the Number Of Gm And Wm Astrocymentioning

confidence: 99%

Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord

Vue

Kim

Parras³

et al. 2014

Development

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Glia constitute the majority of cells in the mammalian central nervous system and are crucial for neurological function. However, there is an incomplete understanding of the molecular control of glial cell development. We find that the transcription factor Ascl1 (Mash1), which is best known for its role in neurogenesis, also functions in both astrocyte and oligodendrocyte lineages arising in the mouse spinal cord at late embryonic stages. Clonal fate mapping in vivo reveals heterogeneity in Ascl1-expressing glial progenitors and shows that Ascl1 defines cells that are restricted to either gray matter (GM) or white matter (WM) as astrocytes or oligodendrocytes. Conditional deletion of Ascl1 post-neurogenesis shows that Ascl1 is required during oligodendrogenesis for generating the correct numbers of WM but not GM oligodendrocyte precursor cells, whereas during astrocytogenesis Ascl1 functions in balancing the number of dorsal GM protoplasmic astrocytes with dorsal WM fibrous astrocytes. Thus, in addition to its function in neurogenesis, Ascl1 marks glial progenitors and controls the number and distribution of astrocytes and oligodendrocytes in the GM and WM of the spinal cord.

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“…6 R, S), although in early rh7 ( Fig. 2 A, C,J ) as well as in the spinal cord Hori et al, 2008;Borromeo et al, 2014) and cerebellum (Millen et al, 2014) Ptf1a-expressing progenitors produce Pax2 ϩ neurons but are not a significant source of Lmx1b ϩ neurons. In Ptf1a Ϫ/Ϫ rh7, Pax2 ϩ dBLa neurons were absent, while dBLb neurons significantly increased in number (ϳ1.8-fold compared with controls, p ϭ 0.0011; Fig.…”

Section: During Late Neurogenesis In Ptf1amentioning

confidence: 94%

Loss ofPtf1aLeads to a Widespread Cell-Fate Misspecification in the Brainstem, Affecting the Development of Somatosensory and Viscerosensory Nuclei

Iskusnykh¹,

Steshina²,

Chizhikov

2016

J. Neurosci.

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The brainstem contains diverse neuronal populations that regulate a wide range of processes vital to the organism. Proper cell-fate specification decisions are critical to achieve neuronal diversity in the CNS, but the mechanisms regulating cell-fate specification in the developing brainstem are poorly understood. Previously, it has been shown that basic helix-loop-helix transcription factor Ptf1a is required for the differentiation and survival of neurons of the inferior olivary and cochlear brainstem nuclei, which contribute to motor coordination and sound processing, respectively. In this study, we show that the loss of Ptf1a compromises the development of the nucleus of the solitary tract, which processes viscerosensory information, and the spinal and principal trigeminal nuclei, which integrate somatosensory information of the face. Combining genetic fate-mapping, birth-dating, and gene expression studies, we found that at least a subset of brainstem abnormalities in Ptf1a Ϫ/Ϫ mice are mediated by a dramatic cell-fate misspecification in rhombomeres 2-7, which results in the production of supernumerary viscerosensory and somatosensory neurons of the Lmx1b lineage at the expense of Pax2 ϩ GABAergic viscerosensory and somatosensory neurons, and inferior olivary neurons. Our data identify Ptf1a as a major regulator of cell-fate specification decisions in the developing brainstem, and as a previously unrecognized developmental regulator of both viscerosensory and somatosensory brainstem nuclei.

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A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord

Cited by 21 publications

References 28 publications

Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus

Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus

Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord

Loss ofPtf1aLeads to a Widespread Cell-Fate Misspecification in the Brainstem, Affecting the Development of Somatosensory and Viscerosensory Nuclei

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