Neural Development最新文献

{"title":"An ancient role for collier/Olf/Ebf (COE)-type transcription factors in axial motor neuron development.","authors":"Catarina Catela,&nbsp;Edgar Correa,&nbsp;Kailong Wen,&nbsp;Jihad Aburas,&nbsp;Laura Croci,&nbsp;G Giacomo Consalez,&nbsp;Paschalis Kratsios","doi":"10.1186/s13064-018-0125-6","DOIUrl":"https://doi.org/10.1186/s13064-018-0125-6","url":null,"abstract":"<p><strong>Background: </strong>Mammalian motor circuits display remarkable cellular diversity with hundreds of motor neuron (MN) subtypes innervating hundreds of different muscles. Extensive research on limb muscle-innervating MNs has begun to elucidate the genetic programs that control animal locomotion. In striking contrast, the molecular mechanisms underlying the development of axial muscle-innervating MNs, which control breathing and spinal alignment, are poorly studied.</p><p><strong>Methods: </strong>Our previous studies indicated that the function of the Collier/Olf/Ebf (COE) family of transcription factors (TFs) in axial MN development may be conserved from nematodes to simple chordates. Here, we examine the expression pattern of all four mouse COE family members (mEbf1-mEbf4) in spinal MNs and employ genetic approaches in both nematodes and mice to investigate their function in axial MN development.</p><p><strong>Results: </strong>We report that mEbf1 and mEbf2 are expressed in distinct MN clusters (termed \"columns\") that innervate different axial muscles. Mouse Ebf1 is expressed in MNs of the hypaxial motor column (HMC), which is necessary for breathing, while mEbf2 is expressed in MNs of the medial motor column (MMC) that control spinal alignment. Our characterization of Ebf2 knock-out mice uncovered a requirement for Ebf2 in the differentiation program of a subset of MMC MNs and revealed for the first time molecular diversity within MMC neurons. Intriguingly, transgenic expression of mEbf1 or mEbf2 can rescue axial MN differentiation and locomotory defects in nematodes (Caenorhabditis elegans) lacking unc-3, the sole C. elegans ortholog of the COE family, suggesting functional conservation among mEbf1, mEbf2 and nematode UNC-3.</p><p><strong>Conclusions: </strong>These findings support the hypothesis that genetic programs controlling axial MN development are deeply conserved across species, and further advance our understanding of such programs by revealing an essential role for Ebf2 in mouse axial MNs. Because human mutations in COE orthologs lead to neurodevelopmental disorders characterized by motor developmental delay, our findings may advance our understanding of these human conditions.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"14 1","pages":"2"},"PeriodicalIF":3.6,"publicationDate":"2019-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13064-018-0125-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36919876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Degeneration of saccular hair cells caused by MITF gene mutation.","authors":"Yi Du,&nbsp;Li-Li Ren,&nbsp;Qing-Qing Jiang,&nbsp;Xing-Jian Liu,&nbsp;Fei Ji,&nbsp;Yue Zhang,&nbsp;Shuo-Long Yuan,&nbsp;Zi-Ming Wu,&nbsp;Wei-Wei Guo,&nbsp;Shi-Ming Yang","doi":"10.1186/s13064-019-0126-0","DOIUrl":"https://doi.org/10.1186/s13064-019-0126-0","url":null,"abstract":"<p><strong>Background: </strong>Waardenburg syndrome (WS) is the consequence of an inherited autosomal dominant mutation which causes the early degeneration of intermediate cells of cochlear stria vascularis (SV) and profound hearing loss. Patients with WS may also experience primary vestibular symptoms. Most of the current WS studies did not discuss the relationship between WS and abnormal vestibular function. Our study found that a spontaneous mutant pig showed profound hearing loss and depigmentation. MITF-M, a common gene mutation causes type WS which affect the development of the intermediate cell of SV, was then identified for animal modeling.</p><p><strong>Results: </strong>In this study, the degeneration of vestibular hair cells was found in pigs with MITF-M. The morphology of hair cells in vestibular organs of pigs was examined using electron microscopy from embryonic day E70 to postnatal two weeks. Significant hair cell loss in the mutant saccule was found in this study through E95 to P14. Conversely, there was no hair cell loss in either utricle or semi-circular canals.</p><p><strong>Conclusions: </strong>Our study suggested that MITF-M gene mutation only affects hair cells of the saccule, but has no effect on other vestibular organs. The study also indicated that the survival of cochlear and saccular hair cells was dependent on the potassium release from the cochlear SV, but hair cells of the utricle and semi-circular canals were independent on SV.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"14 1","pages":"1"},"PeriodicalIF":3.6,"publicationDate":"2019-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13064-019-0126-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36846520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The absence of retinal input disrupts the development of cholinergic brainstem projections in the mouse dorsal lateral geniculate nucleus.","authors":"Guela Sokhadze,&nbsp;Tania A Seabrook,&nbsp;William Guido","doi":"10.1186/s13064-018-0124-7","DOIUrl":"https://doi.org/10.1186/s13064-018-0124-7","url":null,"abstract":"<p><strong>Background: </strong>The dorsal lateral geniculate nucleus (dLGN) of the mouse has become a model system for understanding thalamic circuit assembly. While the development of retinal projections to dLGN has been a topic of extensive inquiry, how and when nonretinal projections innervate this nucleus remains largely unexplored. In this study, we examined the development of a major nonretinal projection to dLGN, the ascending input arising from cholinergic neurons of the brainstem. To visualize these projections, we used a transgenic mouse line that expresses red fluorescent protein exclusively in cholinergic neurons. To assess whether retinal input regulates the timing and pattern of cholinergic innervation of dLGN, we utilized the math5-null (math5^-/-) mouse, which lacks retinofugal projections due to a failure of retinal ganglion cell differentiation.</p><p><strong>Results: </strong>Cholinergic brainstem innervation of dLGN began at the end of the first postnatal week, increased steadily with age, and reached an adult-like pattern by the end of the first postnatal month. The absence of retinal input led to a disruption in the trajectory, rate, and pattern of cholinergic innervation of dLGN. Anatomical tracing experiments reveal these disruptions were linked to cholinergic projections from parabigeminal nucleus, which normally traverse and reach dLGN through the optic tract.</p><p><strong>Conclusions: </strong>The late postnatal arrival of cholinergic projections to dLGN and their regulation by retinal signaling provides additional support for the existence of a conserved developmental plan whereby retinal input regulates the timing and sequencing of nonretinal projections to dLGN.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"13 1","pages":"27"},"PeriodicalIF":3.6,"publicationDate":"2018-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13064-018-0124-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36764210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of early photoreceptor cis-regulatory elements and their relation to Onecut1.","authors":"Nathalie Jean-Charles,&nbsp;Diego F Buenaventura,&nbsp;Mark M Emerson","doi":"10.1186/s13064-018-0121-x","DOIUrl":"https://doi.org/10.1186/s13064-018-0121-x","url":null,"abstract":"<p><strong>Background: </strong>Cone and rod photoreceptors are two of the primary cell types affected in human retinal disease. Potential strategies to combat these diseases are the use of gene therapy to rescue compromised photoreceptors or to generate new functional photoreceptors to replace those lost in the diseased retina. Cis-regulatory elements specific to cones, rods, or both types of photoreceptors are critical components of successful implementation of these two strategies. The purpose of this study was to identify and characterize the cell type specificity and activity of cis-regulatory elements active in developing photoreceptors.</p><p><strong>Methods: </strong>Cis-regulatory elements were introduced into the developing chicken and mouse retina by electroporation. Characterization of reporter activity in relation with cell type markers was determined using confocal microscopy. In addition, two high-throughput flow cytometry assay were developed to assess whether these elements were downstream of Onecut1 in the photoreceptor specification network.</p><p><strong>Results: </strong>The majority of cis-regulatory elements were active in both cone and rod photoreceptors and were largely uninfluenced by a Onecut1 dominant-negative construct. Elements associated with the Thrb, Nr2e3, and Rhodopsin genes showed highly enriched activity in cones or rods, and were affected by interference in Onecut1 signaling. Rhodopsin promoter activity was the most highly influenced by Onecut1 activity and its induction could be modulated by the Maf family transcription factor L-Maf. Nr2e3 elements were observed to have activity in cone photoreceptors and Nr2e3 protein was expressed in developing cone photoreceptors, suggesting a role for this predominant rod gene in cone photoreceptor development.</p><p><strong>Conclusions: </strong>The analysis presented here provides an experimental framework to determine the specificity and strength of photoreceptor elements within specific genetic networks during development. The Onecut1 transcription factor is one such factor that influences the gene regulatory networks specific to cones and rods, but not those that are common to both.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"13 1","pages":"26"},"PeriodicalIF":3.6,"publicationDate":"2018-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13064-018-0121-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36707405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Notch signalling regulates neural stem cell state progression in the Drosophila optic lobe.","authors":"Esteban G Contreras,&nbsp;Boris Egger,&nbsp;Katrina S Gold,&nbsp;Andrea H Brand","doi":"10.1186/s13064-018-0123-8","DOIUrl":"https://doi.org/10.1186/s13064-018-0123-8","url":null,"abstract":"<p><strong>Background: </strong>Neural stem cells generate all of the neurons and glial cells in the central nervous system, both during development and in the adult to maintain homeostasis. In the Drosophila optic lobe, neuroepithelial cells progress through two transient progenitor states, PI and PII, before transforming into neuroblasts. Here we analyse the role of Notch signalling in the transition from neuroepithelial cells to neuroblasts.</p><p><strong>Results: </strong>We observed dynamic regulation of Notch signalling: strong activity in PI progenitors, low signalling in PII progenitors, and increased activity after neuroblast transformation. Ectopic expression of the Notch ligand Delta induced the formation of ectopic PI progenitors. Interestingly, we show that the E3 ubiquitin ligase, Neuralized, regulates Delta levels and Notch signalling activity at the transition zone. We demonstrate that the proneural transcription factor, Lethal of scute, is essential to induce expression of Neuralized and promote the transition from the PI progenitor to the PII progenitor state.</p><p><strong>Conclusions: </strong>Our results show dynamic regulation of Notch signalling activity in the transition from neuroepithelial cells to neuroblasts. We propose a model in which Lethal of scute activates Notch signalling in a non-cell autonomous manner by regulating the expression of Neuralized, thereby promoting the progression between different neural stem cell states.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"13 1","pages":"25"},"PeriodicalIF":3.6,"publicationDate":"2018-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13064-018-0123-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36757603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different Fgfs have distinct roles in regulating neurogenesis after spinal cord injury in zebrafish.","authors":"Yona Goldshmit,&nbsp;Jean Kitty K Y Tang,&nbsp;Ashley L Siegel,&nbsp;Phong D Nguyen,&nbsp;Jan Kaslin,&nbsp;Peter D Currie,&nbsp;Patricia R Jusuf","doi":"10.1186/s13064-018-0122-9","DOIUrl":"https://doi.org/10.1186/s13064-018-0122-9","url":null,"abstract":"<p><strong>Background: </strong>Despite conserved developmental processes and organization of the vertebrate central nervous system, only some vertebrates including zebrafish can efficiently regenerate neural damage including after spinal cord injury. The mammalian spinal cord shows very limited regeneration and neurogenesis, resulting in permanent life-long functional impairment. Therefore, there is an urgent need to identify the cellular and molecular mechanisms that can drive efficient vertebrate neurogenesis following injury. A key pathway implicated in zebrafish neurogenesis is fibroblast growth factor signaling.</p><p><strong>Methods: </strong>In the present study we investigated the roles of distinct fibroblast growth factor members and their receptors in facilitating different aspects of neural development and regeneration at different timepoints following spinal cord injury. After spinal cord injury in adults and during larval development, loss and/or gain of Fgf signaling was combined with immunohistochemistry, in situ hybridization and transgenes marking motor neuron populations in in vivo zebrafish and in vitro mammalian PC12 cell culture models.</p><p><strong>Results: </strong>Fgf3 drives neurogenesis of Islet1 expressing motor neuron subtypes and mediate axonogenesis in cMet expressing motor neuron subtypes. We also demonstrate that the role of Fgf members are not necessarily simple recapitulating development. During development Fgf2, Fgf3 and Fgf8 mediate neurogenesis of Islet1 expressing neurons and neuronal sprouting of both, Islet1 and cMet expressing motor neurons. Strikingly in mammalian PC12 cells, all three Fgfs increased cell proliferation, however, only Fgf2 and to some extent Fgf8, but not Fgf3 facilitated neurite outgrowth.</p><p><strong>Conclusions: </strong>This study demonstrates differential Fgf member roles during neural development and adult regeneration, including in driving neural proliferation and neurite outgrowth of distinct spinal cord neuron populations, suggesting that factors including Fgf type, age of the organism, timing of expression, requirements for different neuronal populations could be tailored to best drive all of the required regenerative processes.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"13 1","pages":"24"},"PeriodicalIF":3.6,"publicationDate":"2018-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13064-018-0122-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36691741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Live imaging of developing mouse retinal slices.","authors":"Anthony P Barrasso,&nbsp;Shang Wang,&nbsp;Xuefei Tong,&nbsp;Audrey E Christiansen,&nbsp;Irina V Larina,&nbsp;Ross A Poché","doi":"10.1186/s13064-018-0120-y","DOIUrl":"https://doi.org/10.1186/s13064-018-0120-y","url":null,"abstract":"<p><strong>Background: </strong>Ex vivo, whole-mount explant culture of the rodent retina has proved to be a valuable approach for studying retinal development. In a limited number of recent studies, this method has been coupled to live fluorescent microscopy with the goal of directly observing dynamic cellular events. However, retinal tissue thickness imposes significant technical limitations. To obtain 3-dimensional images with high quality axial resolution, investigators are restricted to specific areas of the retina and require microscopes, such as 2-photon, with a higher level of depth penetrance. Here, we report a retinal live imaging method that is more amenable to a wider array of imaging systems and does not compromise resolution of retinal cross-sectional area.</p><p><strong>Results: </strong>Mouse retinal slice cultures were prepared and standard, inverted confocal microscopy was used to generate movies with high quality resolution of retinal cross-sections. To illustrate the ability of this method to capture discrete, physiologically relevant events during retinal development, we imaged the dynamics of the Fucci cell cycle reporter in both wild type and Cyclin D1 mutant retinal progenitor cells (RPCs) undergoing interkinetic nuclear migration (INM). Like previously reported for the zebrafish, mouse RPCs in G1 phase migrated stochastically and exhibited overall basal drift during development. In contrast, mouse RPCs in G2 phase displayed directed, apical migration toward the ventricular zone prior to mitosis. We also determined that Cyclin D1 knockout RPCs in G2 exhibited a slower apical velocity as compared to wild type. These data are consistent with previous IdU/BrdU window labeling experiments on Cyclin D1 knockout RPCs indicating an elongated cell cycle. Finally, to illustrate the ability to monitor retinal neuron differentiation, we imaged early postnatal horizontal cells (HCs). Time lapse movies uncovered specific HC neurite dynamics consistent with previously published data showing an instructive role for transient vertical neurites in HC mosaic formation.</p><p><strong>Conclusions: </strong>We have detailed a straightforward method to image mouse retinal slice culture preparations that, due to its relative ease, extends live retinal imaging capabilities to a more diverse group of scientists. We have also shown that, by using a slice technique, we can achieve excellent lateral resolution, which is advantageous for capturing intracellular dynamics and overall cell movements during retinal development and differentiation.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"13 1","pages":"23"},"PeriodicalIF":3.6,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13064-018-0120-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36490137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring.","authors":"Rommel A Santos,&nbsp;Ariel J C Fuertes,&nbsp;Ginger Short,&nbsp;Kevin C Donohue,&nbsp;Hanjuan Shao,&nbsp;Julian Quintanilla,&nbsp;Parinaz Malakzadeh,&nbsp;Susana Cohen-Cory","doi":"10.1186/s13064-018-0118-5","DOIUrl":"https://doi.org/10.1186/s13064-018-0118-5","url":null,"abstract":"<p><strong>Background: </strong>Proper patterning of dendritic and axonal arbors is a critical step in the formation of functional neuronal circuits. Developing circuits rely on an array of molecular cues to shape arbor morphology, but the underlying mechanisms guiding the structural formation and interconnectivity of pre- and postsynaptic arbors in real time remain unclear. Here we explore how Down syndrome cell adhesion molecule (DSCAM) differentially shapes the dendritic morphology of central neurons and their presynaptic retinal ganglion cell (RGC) axons in the developing vertebrate visual system.</p><p><strong>Methods: </strong>The cell-autonomous role of DSCAM, in tectal neurons and in RGCs, was examined using targeted single-cell knockdown and overexpression approaches in developing Xenopus laevis tadpoles. Axonal arbors of RGCs and dendritic arbors of tectal neurons were visualized using real-time in vivo confocal microscopy imaging over the course of 3 days.</p><p><strong>Results: </strong>In the Xenopus visual system, DSCAM immunoreactivity is present in RGCs, cells in the optic tectum and the tectal neuropil at the time retinotectal synaptic connections are made. Downregulating DSCAM in tectal neurons significantly increased dendritic growth and branching rates while inducing dendrites to take on tortuous paths. Overexpression of DSCAM, in contrast, reduced dendritic branching and growth rate. Functional deficits mediated by tectal DSCAM knockdown were examined using visually guided behavioral assays in swimming tadpoles, revealing irregular behavioral responses to visual stimulus. Functional deficits in visual behavior also corresponded with changes in VGLUT/VGAT expression, markers of excitatory and inhibitory transmission, in the tectum. Conversely, single-cell DSCAM knockdown in the retina revealed that RGC axon arborization at the target is influenced by DSCAM, where axons grew at a slower rate and remained relatively simple. In the retina, dendritic arbors of RGCs were not affected by the reduction of DSCAM expression.</p><p><strong>Conclusions: </strong>Together, our observations implicate DSCAM in the control of both pre- and postsynaptic structural and functional connectivity in the developing retinotectal circuit, where it primarily acts as a neuronal brake to limit and guide postsynaptic dendrite growth of tectal neurons while it also facilitates arborization of presynaptic RGC axons cell autonomously.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"13 1","pages":"22"},"PeriodicalIF":3.6,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13064-018-0118-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36492291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic analysis of transcriptional networks directing progression of cell states during MGE development.","authors":"Magnus Sandberg,&nbsp;Leila Taher,&nbsp;Jianxin Hu,&nbsp;Brian L Black,&nbsp;Alex S Nord,&nbsp;John L R Rubenstein","doi":"10.1186/s13064-018-0119-4","DOIUrl":"https://doi.org/10.1186/s13064-018-0119-4","url":null,"abstract":"<p><strong>Background: </strong>Homeodomain (HD) transcription factor (TF) NKX2-1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. NKX2-1 defines MGE regional identity in large part through transcriptional repression, while specification and maturation of GABAergic and cholinergic fates is mediated in part by transcriptional activation via TFs such as LHX6 and LHX8. Here we analyze the signaling and TF pathways, downstream of NKX2-1, required for GABAergic and cholinergic neuron fate maturation.</p><p><strong>Methods: </strong>Differential ChIP-seq analysis was used to identify regulatory elements (REs) where chromatin state was sensitive to change in the Nkx2-1cKO MGE at embryonic day (E) 13.5. TF motifs in the REs were identified using RSAT. CRISPR-mediated genome editing was used to generate enhancer knockouts. Differential gene expression in these knockouts was analyzed through RT-qPCR and in situ hybridization. Functional analysis of motifs within hs623 was analyzed via site directed mutagenesis and reporter assays in primary MGE cultures.</p><p><strong>Results: </strong>We identified 4782 activating REs (aREs) and 6391 repressing REs (rREs) in the Nkx2-1 conditional knockout (Nkx2-1cKO) MGE. aREs are associated with basic-Helix-Loop-Helix (bHLH) TFs. Deletion of hs623, an intragenic Tcf12 aRE, caused a reduction of Tcf12 expression in the sub-ventricular zone (SVZ) and mantle zone (MZ) of the MGE. Mutation of LHX, SOX and octamers, within hs623, caused a reduction of hs623 activity in MGE primary cultures.</p><p><strong>Conclusions: </strong>Tcf12 expression in the SVZ of the MGE is mediated through aRE hs623. The activity of hs623 is dependent on LHX6, SOX and octamers. Thus, maintaining the expression of Tcf12 in the SVZ involves on TF pathways parallel and genetically downstream of NKX2-1.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"13 1","pages":"21"},"PeriodicalIF":3.6,"publicationDate":"2018-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13064-018-0119-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36493965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sympathetic tales: subdivisons of the autonomic nervous system and the impact of developmental studies.","authors":"Uwe Ernsberger,&nbsp;Hermann Rohrer","doi":"10.1186/s13064-018-0117-6","DOIUrl":"10.1186/s13064-018-0117-6","url":null,"abstract":"<p><p>Remarkable progress in a range of biomedical disciplines has promoted the understanding of the cellular components of the autonomic nervous system and their differentiation during development to a critical level. Characterization of the gene expression fingerprints of individual neurons and identification of the key regulators of autonomic neuron differentiation enables us to comprehend the development of different sets of autonomic neurons. Their individual functional properties emerge as a consequence of differential gene expression initiated by the action of specific developmental regulators. In this review, we delineate the anatomical and physiological observations that led to the subdivision into sympathetic and parasympathetic domains and analyze how the recent molecular insights melt into and challenge the classical description of the autonomic nervous system.</p>","PeriodicalId":49764,"journal":{"name":"Neural Development","volume":"13 1","pages":"20"},"PeriodicalIF":3.6,"publicationDate":"2018-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13064-018-0117-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36487537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}