Nuclear Factor I as a Potential Regulator during Postembryonic Organ Development

Puzianowska-Kuźnicka, Monika; Shi, Yun‐Bo

doi:10.1074/jbc.271.11.6273

Cited by 43 publications

(16 citation statements)

References 48 publications

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“…TR and RXR genes are highly activated during late embryogenesis, shortly after tadpole hatching (stages 35 to 36 [48 h]) but well before the synthesis of endogenous T 3 (37). This up-regulation of TR and RXR genes coincides with the down-regulation of several genes, such as the HH (64), ST3 (47), and NF-I genes (51), that are known to be expressed during both metamorphosis and embryogenesis. These genes have also been shown to be up-regulated by T 3 directly at the transcriptional level.…”

Section: Discussionmentioning

confidence: 79%

Both Thyroid Hormone and 9-cis Retinoic Acid Receptors Are Required To Efficiently Mediate the Effects of Thyroid Hormone on Embryonic Development and Specific Gene Regulation in Xenopus laevis

Puzianowska-Kuźnicka

Damjanovski

Shi

1997

Molecular and Cellular Biology

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Tissue culture transfection and in vitro biochemical studies have suggested that heterodimers of thyroid hormone receptors (TRs) and 9-cis retinoic acid receptors (RXRs) are the likely in vivo complexes that mediate the biological effects of thyroid hormone, 3,5,3-triiodothyronine (T 3 ). However, direct in vivo evidence for such a hypothesis has been lacking. We have previously reported a close correlation between the coordinated expression of TR and RXR genes and tissue-dependent temporal regulation of organ transformations during Xenopus laevis metamorphosis. By introducing TRs and RXRs either individually or together into developing Xenopus embryos, we demonstrate here that RXRs are critical for the developmental function of TRs. Precocious expression of TRs and RXRs together but not individually leads to drastic, distinct embryonic abnormalities, depending upon the presence or absence of T 3 , and these developmental effects require the same receptor domains as those required for transcriptional regulation by TR-RXR heterodimers. More importantly, the overexpressed TR-RXR heterodimers faithfully regulate endogenous T 3 response genes that are normally regulated by T 3 only during metamorphosis. That is, they repress the genes in the absence of T 3 and activate them in the presence of the hormone. On the other hand, the receptors have no effect on a retinoic acid (RA) response gene. Thus, RA-and T 3 receptor-mediated teratogenic effects in Xenopus embryos occur through distinct molecular pathways, even though the resulting phenotypes have similarities.Thyroid hormone receptors (TRs) are the nuclear receptors of thyroid hormone, 3,5,3Ј-triiodothyronine (T 3 ) (17,55,69). They belong to the growing family of nuclear hormone receptors, with over 150 identified members, including the receptors for glucocorticoid and RAs (39). Like most other members of this superfamily, TRs are DNA-binding transcription factors whose activities are regulated by their ligand, thyroid hormone. Their DNA binding domain is located in the amino-terminal half of the protein and recognizes specific DNA sequences, i.e., thyroid hormone response elements (TREs). The hormone binding domain is within the carboxyl-terminal half of the protein, which also contains other functional domains, including the AF2 domain, i.e., the transcriptional activation sequence at the carboxyl terminus of the receptor.TRs most likely function as dimers, although they can bind weakly to specific TREs as monomers (18,66,75). In addition, TR homodimers have relatively weak DNA binding affinity compared to the heterodimers formed between TRs and 9-cis RA receptors (RXRs) (26,32,36,41,49,77,78). TR-RXR heterodimers not only bind TREs specifically but also regulate the transcription of T 3 response genes in tissue culture cells with high specificity, implicating that they are the in vivo mediators of the biological effects of T 3 .TR-RXR heterodimers can bind to TREs even in chromatin, both in the presence and absence of T 3 (31,48,61,70).Studies on T 3 -inducible ...

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Section: Discussionmentioning

confidence: 79%

Both Thyroid Hormone and 9-cis Retinoic Acid Receptors Are Required To Efficiently Mediate the Effects of Thyroid Hormone on Embryonic Development and Specific Gene Regulation in Xenopus laevis

Puzianowska-Kuźnicka

Damjanovski

Shi

1997

Molecular and Cellular Biology

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“…Early studies showed that NFI proteins are essential for adenovirus DNA replication both in vitro (1)(2)(3)(4) and in vivo (5,6) and suggested that NFI may function in cellular DNA replication. More recently, expression of the four NFI genes has been shown to be developmentally regulated (7)(8)(9), and NFI proteins have been implicated in the regulation of transcription of genes expressed in many tissues, including liver (10,11), mammary gland (12,13), and brain (14)(15)(16). To assess the role of individual NFI family members in cell growth and development, we have begun a genetic analysis of NFI function in mice.…”

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confidence: 99%

Disruption of the murine nuclear factor I-A gene ( Nfia ) results in perinatal lethality, hydrocephalus, and agenesis of the corpus callosum

Neves

Duchala

Godinho

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

216

240

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The phylogenetically conserved nuclear factor I (NFI) family of transcription/replication proteins is essential both for adenoviral DNA replication and for the transcription of many cellular genes. We showed previously that the four murine NFI genes ( Nfia , Nfib , Nfic, and Nfix ) are expressed in unique but overlapping patterns during mouse development and in adult tissues. Here we show that disruption of the Nfia gene causes perinatal lethality, with >95% of homozygous Nfia −/− animals dying within 2 weeks after birth. Newborn Nfia −/− animals lack a corpus callosum and show ventricular dilation indicating early hydrocephalus. Rare surviving homozygous Nfia −/− mice lack a corpus callosum, show severe communicating hydrocephalus, a full-axial tremor indicative of neurological defects, male-sterility, low female fertility, but near normal life spans. These findings indicate that while the Nfia gene appears nonessential for cell viability and DNA replication in embryonic stem cells and fibroblasts, loss of Nfia function causes severe developmental defects. This finding of an NFI gene required for a developmental process suggests that the four NFI genes may have distinct roles in vertebrate development.

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“…DNA competitors were used at a 100-fold molar excess relative to the DNA probe concentration. Antisera that recognize native NFI proteins (16) or pre-immune rabbit serum were used for supershift assays. Specific mammalian isoforms recognized by the NFI antiserum have not been determined.…”

Section: Methodsmentioning

confidence: 99%

A Role for Nuclear Factor I in the Intrinsic Control of Cerebellar Granule Neuron Gene Expression

Wang

Stock

Gronostajski

et al. 2004

Journal of Biological Chemistry

107

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Nervous system formation requires the elaboration of a complex series of differentiation events in both a spatially and maturation-regulated manner. A fundamental question is how neuronal subtype specification and developmental gene expression are controlled within maturing neurons. The ␣6 subunit of the ␥-aminobutyric acid type A (GABA A ) receptor (GABRA6) is preferentially expressed in cerebellar granule neurons and is part of an intrinsic program directing their differentiation. We have employed a lentiviral approach to examine the transcriptional mechanisms controlling neuronal subtype-selective expression of this gene. These studies demonstrated that nuclear factor I (NFI) proteins are required for both transgenic GABRA6 promoter activity as well as endogenous expression of this gene in cerebellar granule neurons. Chromatin immunoprecipitation also showed that NFI proteins are bound to the GABRA6 promoter in these cells in vivo. Furthermore, analyses of gene knockout mice revealed that Nfia is specifically required for normal expression of the GABRA6 gene in cerebellar granule neurons. NFI expression and DNA binding activity are highly enriched in granule neurons, implicating this transcription factor family in the neuronal subtype-selective expression of the GABRA6 gene. These studies define a new role for NFI proteins as neuronal subtype-enriched transcriptional regulators that participate in an intrinsic transcriptional program directing the differentiation of cerebellar granule neurons.Fundamental to nervous system development is the specification and maturation of diverse neuronal populations that ultimately assemble into a complex synaptic network. These events require the appropriate spatiotemporal expression of an array of different genes during development, and a critical question is the nature of the transcriptional program that controls their proper expression. Several neuron-enriched transcription factors have been directly implicated in the determination of different neuronal populations (1). However, much remains to be learned regarding the roles of individual trans-regulators and their interactions in directing the phenotypes of distinct neuronal subtypes at different phases of their maturation.Cerebellar granule neurons (CGNs) 1 elaborate a well defined terminal differentiation program (2) and provide an excellent model of both cell-specific and developmental regulation of neuronal differentiation. Postnatally, newly born granule neurons migrate from the premigratory zone to form the internal granule cell layer, whereupon dendrite formation and synaptic connections with excitatory mossy fibers and inhibitory Golgi type II neurons ensue. Type A ␣-aminobutyric acid receptors (GABA A R) are present in synaptic and extrasynaptic regions of CGNs associated with inhibitory inputs from Golgi type II cells. During CGN differentiation, GABA A Rs undergo a maturationdependent change from mainly benzodiazepine-sensitive to benzodiazepine-insensitive forms (3). This is associated with a switch in GABA ...

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Nuclear Factor I as a Potential Regulator during Postembryonic Organ Development

Cited by 43 publications

References 48 publications

Both Thyroid Hormone and 9-cis Retinoic Acid Receptors Are Required To Efficiently Mediate the Effects of Thyroid Hormone on Embryonic Development and Specific Gene Regulation in Xenopus laevis

Both Thyroid Hormone and 9-cis Retinoic Acid Receptors Are Required To Efficiently Mediate the Effects of Thyroid Hormone on Embryonic Development and Specific Gene Regulation in Xenopus laevis

Disruption of the murine nuclear factor I-A gene ( Nfia ) results in perinatal lethality, hydrocephalus, and agenesis of the corpus callosum

A Role for Nuclear Factor I in the Intrinsic Control of Cerebellar Granule Neuron Gene Expression

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