Characterization of fetal antigen 1/delta-like 1 homologue expressing cells in the rat nigrostriatal system: effects of a unilateral 6-hydroxydopamine lesion.

Fetal antigen 1/delta-like 1 homologue (FA1/dlk1) belongs to the epidermal growth factor superfamily and is considered to be a non-canonical ligand for the Notch receptor. Interactions between Notch and its ligands are crucial for the development of various tissues. Moreover, FA1/dlk1 has been suggested as a potential supplementary marker of dopaminergic neurons. The present study aimed at investigating the distribution of FA1/dlk1-immunoreactive (-ir) cells in the early postnatal and adult midbrain as well as in the nigrostriatal system of 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian adult rats. FA1/dlk1-ir cells were predominantly distributed in the substantia nigra (SN) pars compacta (SNc) and in the ventral tegmental area. Interestingly, the expression of FA1/dlk1 significantly increased in tyrosine hydroxylase (TH)-ir cells during early postnatal development. Co-localization and tracing studies demonstrated that FA1/dlk1-ir cells in the SNc were nigrostriatal dopaminergic neurons, and unilateral 6-OHDA lesions resulted in loss of both FA1/dlk1-ir and TH-ir cells in the SNc. Surprisingly, increased numbers of FA1/dlk1-ir cells (by 70%) were detected in dopamine-depleted striata as compared to unlesioned controls. The higher number of FA1/dlk1-ir cells was likely not due to neurogenesis as colocalization studies for proliferation markers were negative. This suggests that FA1/dlk1 was up-regulated in intrinsic cells in response to the 6-OHDA-mediated loss of FA1/dlk1-expressing SNc dopaminergic neurons and/or due to the stab wound. Our findings hint to a significant role of FA1/dlk1 in the SNc during early postnatal development. The differential expression of FA1/dlk1 in the SNc and the striatum of dopamine-depleted rats could indicate a potential involvement of FA1/dlk1 in the cellular response to the degenerative processes.

FZD6, MATN2 AND SLC25A32, POSSIBLE CANDIDATE GENES IN NONSYNDROMIC CLEFT LIP AND PALATE

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with a multifactorial etiology. Despite decades of research, the genetic underpinnings of NSCLP still remain largely unexplained. A genome wide association study (GWAS) of a large NSCLP African American family with seven affected individuals across three generations found evidence for linkage at 8q21.3-24.12 (LOD = 2.98). This region contained three biologically relevant candidate genes: Frizzled-6 (FZD6) (LOD = 2.8), Matrilin-2 (MATN2) (LOD = 2.3), and Solute Carrier Family 25, Member 32 (SLC26A32) (LOD = 1.6). Sequencing of the coding regions and the 5’ and 3’ UTRs of these genes in two affected family members identified a rare intronic variant, rs138557689 (c.-153+432A>C), in FZD6. The rs138557689/C allele segregated with the NSCLP phenotype; in silico analysis predicted and EMSA analysis showed that the 138557689/C allele creates new DNA binding sites. FZD6 is part of the WNT pathway, which is involved in craniofacial development, including midface development and upper lip fusion. Our novel findings suggest that an alteration in FZD6 gene regulation may perturb this tightly controlled biological pathway and in turn contribute to the development of NSCLP in this family. Studies are underway to further define how the rs138557689/C variant affects expression of FZD6.

The identification and regulation of a novel interaction occurring between $\beta$-catenin and the actin -bundling protein fascin

Catenins were first characterized as linking the cytoplasmic domains of cadherin cell-cell adhesion molecules to the cortical actin cytoskeleton. In addition to their essential role in modulating cadherin adhesion, catenins have more recently been indicated to participate in cell and developmental signaling pathways. $\beta$-catenin, for example, associates directly with receptor tyrosine kinases and transcription factors such as LEF-1/TCF, and tranduces developmental signals within the Wnt pathway. $\beta$-catenin also appear to a role in regulating cell proliferation via its interaction with the tumor supressor protein APC. I have employed the yeast two-hybrid method to reveal that fascin, a bundler of actin filaments, binds to $\beta$-catenin's central Armadillo-repeat domain. The $\beta$-catenin-fascin interaction exists in cell lines as well as in animal brain tissues as revealed by immunoprecipitation analysis, and substantiated in vitro with purified proteins. Fascin additionally binds to plakoglobin, which contains a more divergent Armadillo-repeat domain. Fascin and E-cadherin utilize a similar binding-site within $\beta$-catenin, such that they form mutually exclusive complexes with $\beta$-catenin. Fascin and $\beta$-catenin co-localize at cell-cell borders and dynamic cell leading edges of epithelial and endothelial cells. Total immunoprecipitable b-catein has several isoforms, only the hyperphosphorylated isoform 1 associated with fascin. An increased $\beta$-catenin-fascin interaction was observed in HGF stimulated cells, and in Xenopus embryos injected with src kinase RNAs. The increased $\beta$-catenin association with fascin is correlated with increased levels of $\beta$-catenin phosphorylation. $\beta$-catenin, but not fascin, can be readily phosphorylated on tyrosine in vivo following src injection of embryos, or in vitro following v-src addition to purified protein components. These observations suggest a role of $\beta$-catenin phosphorylation in regulating its interaction with fascin, and src kinase may be an important regulator of the $\beta$-catenin-fascin association in vivo. The $\beta$-catenin-fascin interaction represents a novel catenin complex, that may conceivably regulate actin cytoskeletal structures, cell adhesion, and cellular motility, perhaps in a coordinate manner with its functions in cadherin and APC complexes. ^

Conflict and cognitive control during sentence comprehension: recruitment of a frontal network during the processing of Spanish object-first sentences.

During sentence processing there is a preference to treat the first noun phrase found as the subject and agent, unless marked the other way. This preference would lead to a conflict in thematic role assignment when the syntactic structure conforms to a non-canonical object-before-subject pattern. Left perisylvian and fronto-parietal brain networks have been found to be engaged by increased computational demands during sentence comprehension, while event-reated brain potentials have been used to study the on-line manifestation of these demands. However, evidence regarding the spatiotemporal organization of brain networks in this domain is scarce. In the current study we used Magnetoencephalography to track spatio-temporally brain activity while Spanish speakers were reading subject- and object-first cleft sentences. Both kinds of sentences remained ambiguous between a subject-first or an object-first interpretation up to the appearance of the second argument. Results show the time-modulation of a frontal network at the disambiguation point of object-first sentences. Moreover, the time windows where these effects took place have been previously related to thematic role integration (300–500 ms) and to sentence reanalysis and resolution of conflicts during processing (beyond 500 ms post-stimulus). These results point to frontal cognitive control as a putative key mechanism which may operate when a revision of the sentence structure and meaning is necessary

La deformación del tipo Construcción de bóvedas no-canónicas en España (siglos XVI-XVIII)

Una bóveda no canónica es una bóveda que se adapta a una forma distinta de aquella para la que ha sido inicialmente concebida. Bóvedas raras, anormales, no convencionales, habitualmente consideradas excepciones o casos particulares, resultan ser más frecuentes de lo inicialmente esperado. El interés por este tipo de bóvedas surge a raíz de una investigación inicial sobre las bóvedas empleadas para cubrir espacios de planta anular, como en el caso de las girolas de las iglesias. Sin embargo, el problema de la bóveda anular no puede ser abordado directamente, sino como parte de una investigación más general sobre bóvedas que se deforman para adaptarse a una situación anómala. El análisis de las posibilidades que un determinado tipo de bóveda brinda para resolver el abovedamiento de espacios de planta irregular, trascendiendo el problema de la planta anular, es lo que da origen a esta investigación. La cuestión de las bóvedas deformadas forma parte de un contexto mayor, el de la deformación en arquitectura abovedada. Ante una contradicción, la deformación de la bóveda es sólo una de las posibles opciones que esta arquitectura ofrece para resolver un problema de deformación. La tesis se estructura en dos partes: en la primera parte se analizan los conceptos de forma y deformación en el contexto de la arquitectura abovedada con objeto de sentar las bases para una teoría de las bóvedas no canónicas. El objetivo es establecer un punto de partida para la investigación en un campo que todavía no había sido abordado. En la segunda parte se analizan tres tipos de bóveda desde la perspectiva de las bóvedas no canónicas, a partir de un estudio de casos de bóvedas en España entre los siglos XVI y XVIII. El estudio de la deformación en arquitectura abovedada se centra en el problema de la girola, por tratarse de un caso generalizado de deformación, directamente relacionado con el problema de las bóvedas irregulares y cuyo estudio, llamativamente, no había sido llevado a cabo hasta la fecha. Se propone una primera aproximación al problema de la girola, desde un punto de vista puramente morfológico, al margen de consideraciones históricas. En el caso de las bóvedas deformadas, el análisis se centra en tres tipos de bóveda: la bóveda de crucería, la bóveda de arista y la bóveda baída. Estos tres tipos de bóveda, aunque basadas en criterios formales distintos, están íntimamente relacionados entre sí. Por un lado permiten resolver el mismo problema –planta cuadrada delimitada por arcos–, por otro lado es posible establecer una relación formal entre la bóveda de arista y la bóveda baída a través de la bóveda de crucería. El estudio de casos recogido en la segunda parte de la tesis se fundamenta en dos líneas de investigación, la primera sobre soluciones teóricas de bóvedas no convencionales propuestas en los manuscritos y tratados de cantería, y la segunda sobre bóvedas efectivamente construidas, tratado de establecer una comparación entre teoría y práctica, confrontando el grado de relación entre ambas. Sin embargo este doble análisis sólo se ha podido llevar a cabo en contadas ocasiones. Constatamos que las bóvedas no canónicas reflejadas en los tratados son pocas y apenas se han llevado a la práctica, mientras que las soluciones construidas no responden a modelos teóricos propuestos, manifestando un divorcio entre teoría y práctica. El estudio de estas bóvedas permite poner en cuestión la definición tradicional que relaciona los conceptos de ‘bóveda’ y ‘superficie’. Al iniciar el trabajo nos encontramos con un modelo teórico extremadamente rígido que deja fuera un gran número de bóvedas, obligando a agruparlas bajo el término «no canónicas». El trabajo realizado pone en evidencia lo limitado del modelo. El problema no está en la presencia de bóvedas anómalas, que no se adaptan al modelo tradicionalmente propuesto, sino en la extrema rigidez del modelo. ABSTRACT A non canonical vault is a vault adapted to a different form from that for which was originally conceived. These rare, abnormal, unconventional vaults are usually considered as exceptions or special cases. However they prove to be more frequent than it was initially expected. Interest in this type of vaults arises from an initial research on the vaults used to roof annular spaces, such as ambulatories. Nevertheless, the annular vault question cannot be addressed directly, but as a part of a broader research on distorted vaults; a research on vaults deformed to conform an anomalous layout. The analysis of the possibilities that a particular type of vault provides to solve the vaulting of an irregular layout, beyond the problem of the annular plan is the origin of this research. The argument of deformed vaults is part of a greater context, the context of deformation in vaulted architecture. Facing a contradiction, deforming a vault is just one of the options that vaulted architecture offers to solve a problem of deformation. This dissertation is organised in two parts: in the first part we analyse the concepts of form and deformation in the context of vaulted architecture in order to lay the foundations for a non canonical vaults theory. The objective is to establish a starting point for future research in a field that has not been addressed yet. In the second part, we analyse three types of vault from the perspective of non canonical vaults, based on a case study of Spanish vaults between the 16th and 18th Centuries. The analysis of deformation in vaulted architecture focuses on the question of the ambulatory, because it is a generalized example of deformation, directly related to the problem of irregular vaults. Remarkably, the analysis of these spaces had not been conducted to date. We propose a first approach to the question of the ambulatory, from a purely morphological point of view, setting aside historical considerations. The analysis of deformed vaults focuses on three types of vault: the groin vault, the ribbed vault and the sail vault. These three types of vault, although based on different formal criteria, are closely related between them. On the one hand, they allow to solve the same problem –a square perimeter limited by arcs-; on the other hand, it is possible to establish a formal relationship between the groin vault and the sail vault through the ribbed vault. The case study presented in the second part of this dissertation is based on two research lines: theoretical non conventional vaults solutions proposed on stonecutting treatises; and currently built vaults. The aim of this double analysis was to establish a comparison between theory and practice, comparing the degree of relationship between them. Nevertheless, this double analysis has only been carried out on rare occasions. It is noted that non canonical vaults reflected in treaties are few and hardly been employed, while the built solutions do not meet proposed theoretical models, expressing a divorce between theory and practice. The analysis of these vaults allows us to question the traditional definition that connects the concepts of 'vault' and 'surface'. When we began this research, we found an extremely rigid theoretical model that leaved out many vaults, forcing to group them under the term of «non canonical vaults». This research evidences the limitations of the model. The problem is not the presence of abnormal vaults, which cannot adapt to the traditional model, but in the very high stiffness of the model.

Siamois is required for formation of Spemann’s organizer

Spemann’s organizer develops in response to dorsal determinants that act via maternal components of the wnt pathway. The function of siamois, a wnt-inducible homeobox gene, in Spemann’s organizer development was examined by fusion of defined transcriptional regulatory domains to the siamois homeodomain. Similar to native siamois, a VP16 activator fusion induced axis formation, indicating that siamois functions as a transcriptional activator in axis induction. Fusion of the engrailed repressor generated a dominant inhibitor that blocked axis induction by Xwnt8, β-catenin, and siamois, and repressed wnt activation of the goosecoid promoter. Dorsal injection of the engrailed-siamois fusion resulted in complete inhibition of dorsal development and organizer gene expression, an effect rescued by siamois, but not by Xwnt8 or β-catenin. Thus, as a zygotic mediator of maternal dorsal signals, siamois function is required for development of Spemann’s organizer.

Methylation by a mutant T2 DNA [N6-adenine] methyltransferase expands the usage of RecA-assisted endonuclease (RARE) cleavage

Properties of a mutant bacteriophage T2 DNA [N6-adenine] methyltransferase (T2 Dam MTase) have been investigated for its potential utilization in RecA-assisted restriction endonuclease (RARE) cleavage. Steady-state kinetic analyses with oligonucleotide duplexes revealed that, compared to wild-type T4 Dam, both wild-type T2 Dam and mutant T2 Dam P126S had a 1.5-fold higher kcat in methylating canonical GATC sites. Additionally, T2 Dam P126S showed increased efficiencies in methylation of non-canonical GAY sites relative to the wild-type enzymes. In agreement with these steady-state kinetic data, when bacteriophage λ DNA was used as a substrate, maximal protection from restriction nuclease cleavage in vitro was achieved on the sequences GATC, GATN and GACY, while protection of GACR sequences was less efficient. Collectively, our data suggest that T2 Dam P126S can modify 28 recognition sequences. The feasibility of using the mutant enzyme in RARE cleavage with BclI and EcoRV endonucleases has been shown on phage λ DNA and with BclI and DpnII endonucleases on yeast chromosomal DNA embedded in agarose.

The length of telomeric G-rich strand 3′-overhang measured by oligonucleotide ligation assay

A typical G-rich telomeric DNA strand, which runs 5′→3′ toward the chromosome ends, protrudes by several nucleotides in lower eukaryotes. In human chromosomes long G-rich 3′-overhangs have been found. Apart from the standard G-rich tail, several non-canonical terminal structures have been proposed. However, the mechanism of long-tail formation, the presence and the role of these structures in telomere maintenance or shortening are not completely understood. In a search for a simple method to accurately measure the 3′-overhang we have established a protocol based on the ligation of telomeric oligonucleotide hybridized to non-denatured DNA under stringent conditions (oligonucleotide ligation assay with telomeric repeat oligonucleotide). This method enabled us to detect a large proportion of G-rich single-stranded telomeric DNA that was as short as 24 nt. Nevertheless, we showed G-tails longer than 400 nt. In all tested cells the lengths ranging from 108 to 270 nt represented only 37% of the whole molecule population, while 56–62% were <90 nt. Our protocol provides a simple and sensitive method for measuring the length of naturally occurring unpaired repeated DNA.

Inhibitory Control is a Rate-Limiting Factor to Preschoolers' Use of Irregular Inflection

We investigated whether children’s inhibitory control is associated with their ability to produce irregular verb forms as well as learn from corrective feedback following their use of an over-regularized form. Forty-eight 3.5 to 4.5 year old children were tested on the irregular past tense and provided with adult corrective input via models of correct use or recasts of errors following ungrammatical responses. Inhibitory control was assessed with a three-item battery of tasks that required suppressing a prepotent response in favor of a non-canonical one. Results showed that inhibitory control was predictive of children’s initial production of irregular forms and not associated with their post-feedback production of irregulars. These findings show that children’s executive functioning skills may be a rate-limiting factor on their ability to produce correct forms, but might not interact with their ability to learn from input in this domain. Findings are discussed in terms of current theories of past-tense acquisition and learning from input more broadly.

Vital Subjects: Race and Biopolitics in Italy, (1860-1920) /

Vital Subjects: Race and Biopolitics in Italy is an interdisciplinary study of how racial and colonial discourses shaped the “making” of Italians as modern political subjects in the years between its administrative unification (1861-1870) and the end of the First World War (1919)

Limitations of the widely used GAM42a and BET42a probes targeting bacteria in the Gammaproteobacteria radiation

The 23S rRNA-targeted probes GAM42a and BET42a provided equivocal results with the uncultured gammaproteobacterium 'Candidatus Competibacter phosphatis' where some cells bound GAM42a and other cells bound BET42a in fluorescence in situ hybridization (FISH) experiments. Probes GAM42a and BET42a span positions 1027-1043 in the 23S rRNAand differ from each other by one nucleotide at position 1033. Clone libraries were prepared from PCR products spanning the 16S rRNA genes, intergenic spacer region and 23S rRNA genes from two mixed cultures enriched in 'Candidatus C. phosphatis'. With individual clone inserts, the 16S rDNA portion was used to confirm the source organism as 'Candidatus C. phosphatis' and the 23S rDNA portion was used to determine the sequence of the GAM42a/BET42a probe target region. Of the 19 clones sequenced, 8 had the GAM42a probe target (T at position 1033) and 11 had G at position 1033, the only mismatch with GAM42a. However, none of the clones had the BET42a probe target (A at 1033). Non-canonical base-pairing between the 23S rRNA of 'Candidatus C. phosphatis' with G at position 1033 and GAM42a (G-A) or BET42a (G-T) is likely to explain the probing anomalies. A probe (GAM42_C1033) was optimized for use in FISH, targeting cells with G at position 1033, and was found to highlight not only some 'Candidatus C. phosphatis' cells, but also other bacteria. This demonstrates that there are bacteria in addition to 'Candidatus C. phosphatis' with the GAM42_C1033 probe target and not the BET42a or GAM42a probe target.

DE SIMPLES MOTORISTA A SANTO. PERSPECTIVAS FOLKCOMUNICACIONAIS EM RELIGIÃO E CULTURA POPULAR NO CASO DO MOTORISTA GREGÓRIO , UM SANTO DO PIAUÍ

Este estudo analisa o processo comunicacional em torno das manifestações populares e da história do santo não-canônico piauiense Motorista Gregório. O objetivo geral consistiu em observar, analisar e relacionar a comunicação popular que faz parte do processo à consolidação da figura do milagreiro. As teorias da cultura, especialmente a Folkcomunicação, assim como as da linguagem, configuraram-se referenciais relevantes nas análises das formas de comunicação dos devotos e dos jornais impressos de Teresina. Para isso, utilizou-se uma combinação de metodologias tais como a de Marques de Melo (2008) para inventariar os ex-votos, além de entrevistas semiestruturadas, coleta de depoimentos e observação participante para reunir dados e classificar as informações obtidas. A análise revelou que a oralidade é a forma de comunicação mais utilizada e que mais tem influencia sobre os devotos, que os jornais impressos reproduzem as histórias do povo e que o santo é criado e formado no cotidiano, no convívio dos familiares, vizinhos e amigos.

Amino acid, peptide and drug transport across monolayers of human intestinal (CAC0-2) cells in vitro

The properties of Caco-2 monolayers were compared on aluminium oxide and nitrocellulose permeable-supports. On nitrocellulose, Caco-2 cells displayed a higher rate of taurocholic acid transport than those cultured on aluminium oxide inserts. In addition, Caco-2 cells grown on these two inserts were not comparable with respect to cell morphology, cell numbers and transepithelial electrical resistance. The low adsorption potential of the aluminium oxide inserts, particularly for high molecular weight or lipophilic ligands, offers a distinct advantage over nitrocellulose inserts for drug transport studies. The carrier-mediated uptake and transport of the imino acid (L-proline) and the acidic amino acids (L-aspartate and L-glutamate) have been studied. At pH7.4, L-proline uptake is mediated via an A-system carrier. Elevated uptake and transport under acidic conditions occurs by activation of a distinct carrier population. Acidic amino acid transport is mediated via a X-AG system. The flux of baclofen, CGP40116 andCGP40117 across Caco-2 monolayers was described by passive transport. The transport of three peptides, thyrotrophin-releasing hormone, SQ29852 and cyclosporin were investigated. Thyrotrophin-releasing hormone transport acrossCaco-2 monolayers was characterised by a minor saturable (carrier-mediated,approximately 25%) pathway, superimposed onto a major non-saturable (diffusional)pathway. SQ29852 uptake into Caco-2 monolayers is described by a major saturable mechanism (Km = 0.91 mM) superimposed onto a minor passive component.However, the initial-rate of SQ29852 transport is consistent with a passive transepithelial transport mechanism. These data highlight the possibility that itsbasolateral efflux is severely retarded such that the passive paracellular transportdictates the overall transepithelial transport characteristics. In addition, modelsuitable for investigating the transepithelial transport of cyclosporin A has been developed. A modification of the conventional Caco-2 model has been developed which has a calcium-free Ap donor-solution and a Bl receiver-solution containing the minimumcalcium concentration required to maintain monolayer integrity (100 μM). The influence of calcium and magnesium on the absorption of [14C]pamidronate was evaluated by comparing its transport across the conventional and minimum calciumCaco-2 models. Ap calcium and magnesium ions retard the Ap-to-Bl flux of pamidronate across Caco-2 monolayers. The effect of self-emulsifying oleic acid-Tween 80 formulations on Caco-2monolayer integrity has been investigated. Oleic acid-Tween 80 (1 0:1) formulations produced a dose-dependent disruption of Caco-2 monolayer integrity. This disruption was related to the oleic acid content of the formulation.

Glutaredoxin-1 up-regulation induces soluble vascular endothelial growth factor receptor 1, attenuating post-ischemia limb revascularization

Glutaredoxin-1 (Glrx) is a cytosolic enzyme that regulates diverse cellular function by removal of GSH adducts from S-glutathionylated proteins including signaling molecules and transcription factors. Glrx is up-regulated during inflammation and diabetes. Glrx overexpression inhibits VEGF-induced endothelial cell (EC) migration. The aim was to investigate the role of up-regulated Glrx in EC angiogenic capacities and in vivo revascularization in the setting of hind limb ischemia. Glrx overexpressing EC from Glrx transgenic mice (TG) showed impaired migration and network formation and secreted higher level of soluble VEGF receptor 1 (sFlt), an antagonizing factor to VEGF. After hind limb ischemia surgery Glrx TG mice demonstrated impaired blood flow recovery, associated with lower capillary density and poorer limb motor function compared to wild type littermates. There were also higher levels of anti-angiogenic sFlt expression in the muscle and plasma of Glrx TG mice after surgery. Non-canonical Wnt5a is known to induce sFlt. Wnt5a was highly expressed in ischemic muscles and EC from Glrx TG mice, and exogenous Wnt5a induced sFlt expression and inhibited network formation in human microvascular EC. Adenoviral Glrx-induced sFlt in EC was inhibited by a competitive Wnt5a inhibitor. Furthermore, Glrx overexpression removed GSH adducts on p65 in ischemic muscle and EC, and enhanced nuclear factor kappa B (NF-kB) activity which was responsible for Wnt5a-sFlt induction. Taken together, up-regulated Glrx induces sFlt in EC via NF-kB -dependent Wnt5a, resulting in attenuated revascularization in hind limb ischemia. The Glrx-induced sFlt may be a part of mechanism of redox regulated VEGF signaling.

The development and growth of tissues derived from cranial neural crest and primitive mesoderm is dependent on the ligation status of retinoic acid receptor γ:evidence that retinoic acid receptor γ functions to maintain stem/progenitor cells in the absence of retinoic acid

Retinoic acid (RA) signaling is important to normal development. However, the function of the different RA receptors (RARs)-RARα, RARβ, and RARγ-is as yet unclear. We have used wild-type and transgenic zebrafish to examine the role of RARγ. Treatment of zebrafish embryos with an RARγ-specific agonist reduced somite formation and axial length, which was associated with a loss of hoxb13a expression and less-clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist also disrupted formation of tissues arising from cranial neural crest, including cranial bones and anterior neural ganglia. There was a loss of Sox 9-immunopositive neural crest stem/progenitor cells in the same anterior regions. Pectoral fin outgrowth was blocked by RARγ agonist treatment. However, there was no loss of Tbx-5-immunopositive lateral plate mesodermal stem/progenitor cells and the block was reversed by agonist washout or by cotreatment with an RARγ antagonist. Regeneration of the caudal fin was also blocked by RARγ agonist treatment, which was associated with a loss of canonical Wnt signaling. This regenerative response was restored by agonist washout or cotreatment with the RARγ antagonist. These findings suggest that RARγ plays an essential role in maintaining stem/progenitor cells during embryonic development and tissue regeneration when the receptor is in its nonligated state.