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Article ; Online: Transcription factors and effectors that regulate neuronal morphology.

Santiago, Celine / Bashaw, Greg J

2014 Volume 141, Issue 24, Page(s) 4667–4680

Abstract: ... transcription factors and the downstream effectors through which they regulate neural connectivity in multiple model ... of neural circuit assembly, few have identified the downstream effectors by which they control neuronal ... by regulating the expression of genes that give a cell its morphological and functional properties ...

Abstract	Transcription factors establish the tremendous diversity of cell types in the nervous system by regulating the expression of genes that give a cell its morphological and functional properties. Although many studies have identified requirements for specific transcription factors during the different steps of neural circuit assembly, few have identified the downstream effectors by which they control neuronal morphology. In this Review, we highlight recent work that has elucidated the functional relationships between transcription factors and the downstream effectors through which they regulate neural connectivity in multiple model systems, with a focus on axon guidance and dendrite morphogenesis.
MeSH term(s)	Animals ; Axons/physiology ; Dendrites/physiology ; Gene Expression Regulation, Developmental/physiology ; Humans ; Models, Neurological ; Neurogenesis/physiology ; Neurons/cytology ; Neurons/metabolism ; Receptors, Cell Surface/metabolism ; Transcription Factors/metabolism
Chemical Substances	Receptors, Cell Surface ; Transcription Factors
Language	English
Publishing date	2014-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.110817
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Article: Anxiolytic and Anxiogenic? How the Transcription Factor MEF2 Might Explain the Manifold Behavioral Effects of Oxytocin.

Jurek, Benjamin / Meyer, Magdalena

Frontiers in endocrinology

2020 Volume 11, Page(s) 186

Abstract: ... cellular morphology and connectivity, MEF2 is one of the key factors that might contribute to the diverse ... transcription and translation has been identified. Those oxytocin-driven effectors, such as MEF2 and CREB, are ... molecular level, a set of oxytocin receptor-coupled signaling cascades and downstream effectors regulating ...

Abstract	The neuromodulator oxytocin, since its first synthesis by du Vigneaud in 1953, has mainly been associated with beneficial physiological effects, as well as positive social and emotional behaviors. This overall positive picture of oxytocin as the "love-, cuddle-, or bonding-hormone" has repeatedly been challenged since then. Oxytocin-induced effects that would be perceived as negative by the individual, such as increased anxiety or potentiation of stress-induced ACTH release, as well as the regulation of negative approach-related emotions, such as envy and schadenfreude (gloating) have been described. The general consent is that oxytocin, instead of acting unidirectional, induces changes in the salience network to shift the emphasis of emotional contexts, and therefore can, e.g., produce both anxiolytic as well as anxiogenic behavioral outcomes. However, the underlying mechanisms leading to alterations in the salience network are still unclear. With the aim to understand the manifold effects of oxytocin on a cellular/molecular level, a set of oxytocin receptor-coupled signaling cascades and downstream effectors regulating transcription and translation has been identified. Those oxytocin-driven effectors, such as MEF2 and CREB, are known modulators of the neuronal and glial cytoarchitecture. We hypothesize that, by determining cellular morphology and connectivity, MEF2 is one of the key factors that might contribute to the diverse behavioral effects of oxytocin.
MeSH term(s)	Animals ; Anti-Anxiety Agents/pharmacology ; Anxiety/chemically induced ; Behavior/drug effects ; Behavior, Animal/drug effects ; Emotions/drug effects ; Humans ; MEF2 Transcription Factors/physiology ; Oxytocin/adverse effects ; Oxytocin/pharmacology ; Signal Transduction/drug effects ; Signal Transduction/genetics
Chemical Substances	Anti-Anxiety Agents ; MEF2 Transcription Factors ; Oxytocin (50-56-6)
Language	English
Publishing date	2020-04-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2020.00186
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Article ; Online: The homeodomain transcription factor Hb9 controls axon guidance in Drosophila through the regulation of Robo receptors.

Santiago, Celine / Labrador, Juan-Pablo / Bashaw, Greg J

Cell reports

2014 Volume 7, Issue 1, Page(s) 153–165

Abstract: ... we show that the homeodomain transcription factor Hb9 acts upstream of Robo2 and Robo3 to regulate axon ... Transcription factors establish neural diversity and wiring specificity; however, how ... its conserved repressor domain and functions in parallel with Nkx6 to regulate robo2. Moreover, hb9 can regulate ...

Abstract	Transcription factors establish neural diversity and wiring specificity; however, how they orchestrate changes in cell morphology remains poorly understood. The Drosophila Roundabout (Robo) receptors regulate connectivity in the CNS, but how their precise expression domains are established is unknown. Here, we show that the homeodomain transcription factor Hb9 acts upstream of Robo2 and Robo3 to regulate axon guidance in the Drosophila embryo. In ventrally projecting motor neurons, hb9 is required for robo2 expression, and restoring Robo2 activity in hb9 mutants rescues motor axon defects. Hb9 requires its conserved repressor domain and functions in parallel with Nkx6 to regulate robo2. Moreover, hb9 can regulate the medio-lateral position of axons through robo2 and robo3, and restoring robo3 expression in hb9 mutants rescues the lateral position defects of a subset of neurons. Altogether, these data identify Robo2 and Robo3 as key effectors of Hb9 in regulating nervous system development.
MeSH term(s)	Animals ; Axons/metabolism ; Drosophila ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Neurogenesis/physiology ; Neurons/metabolism ; Neurons/physiology ; Receptors, Immunologic/genetics ; Receptors, Immunologic/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Drosophila Proteins ; Homeodomain Proteins ; Receptors, Immunologic ; Robo2 protein, Drosophila ; Transcription Factors ; exex protein, Drosophila ; robo3 protein, Drosophila
Language	English
Publishing date	2014-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2014.02.037
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Article ; Online: Dlx1 transcription factor regulates dendritic growth and postsynaptic differentiation through inhibition of neuropilin-2 and PAK3 expression.

Dai, Xiaojing / Iwasaki, Hirohide / Watanabe, Masahiko / Okabe, Shigeo

The European journal of neuroscience

2014 Volume 39, Issue 4, Page(s) 531–547

Abstract: ... of possible downstream effectors of Dlx1, neuropilin-2 and p21-activated kinase 3, we provided evidence ... postsynaptic differentiation, we manipulated Dlx1 expression in both excitatory pyramidal neurons and ... important downstream regulators, leading to the characteristic morphology of Dlx1-expressing interneurons ...

Abstract	Dlx1, a member of the homeobox domain transcriptional factors, is expressed in a subset of interneurons and is involved in their differentiation. To understand the roles of Dlx1 in dendritic and postsynaptic differentiation, we manipulated Dlx1 expression in both excitatory pyramidal neurons and inhibitory interneurons in hippocampal culture. Exogenous expression of Dlx1 in pyramidal neurons, which lack endogenous Dlx1, resulted in reduced complexity of dendritic arborization. This effect was dependent on the DNA-binding motif of Dlx1. Dlx1 overexpression also induced prominent reduction of spine density, but with mild suppression in the formation of postsynaptic densities. To confirm the roles of endogenous Dlx1, we knocked down Dlx1 in interneurons and found enhanced dendritic growth. By manipulating the expression of possible downstream effectors of Dlx1, neuropilin-2 and p21-activated kinase 3, we provided evidence for the involvement of these two signaling molecules in Dlx1-dependent regulation of dendritic differentiation. Our experimental data support the idea that Dlx1 expression in developing interneurons specifically suppresses two important downstream regulators, leading to the characteristic morphology of Dlx1-expressing interneurons with less branched dendrites and few dendritic spines.
MeSH term(s)	Animals ; Cells, Cultured ; Dendrites/metabolism ; Dendrites/physiology ; Hippocampus/cytology ; Hippocampus/growth & development ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Interneurons/cytology ; Interneurons/metabolism ; Mice ; Mice, Inbred ICR ; Neurogenesis ; Neuropilin-2/genetics ; Neuropilin-2/metabolism ; Post-Synaptic Density/metabolism ; Pyramidal Cells/cytology ; Pyramidal Cells/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; p21-Activated Kinases/genetics ; p21-Activated Kinases/metabolism
Chemical Substances	Distal-less homeobox proteins ; Homeodomain Proteins ; Neuropilin-2 ; Transcription Factors ; Pak3 protein, mouse (EC 2.7.11.1) ; p21-Activated Kinases (EC 2.7.11.1)
Language	English
Publishing date	2014-02
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.12413
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Article ; Online: The Homeodomain Transcription Factor Hb9 Controls Axon Guidance in Drosophila through the Regulation of Robo Receptors

Celine Santiago / Juan-Pablo Labrador / Greg J. Bashaw

Cell Reports, Vol 7, Iss 1, Pp 153-

2014 Volume 165

Abstract	Transcription factors establish neural diversity and wiring specificity; however, how they orchestrate changes in cell morphology remains poorly understood. The Drosophila Roundabout (Robo) receptors regulate connectivity in the CNS, but how their precise expression domains are established is unknown. Here, we show that the homeodomain transcription factor Hb9 acts upstream of Robo2 and Robo3 to regulate axon guidance in the Drosophila embryo. In ventrally projecting motor neurons, hb9 is required for robo2 expression, and restoring Robo2 activity in hb9 mutants rescues motor axon defects. Hb9 requires its conserved repressor domain and functions in parallel with Nkx6 to regulate robo2. Moreover, hb9 can regulate the medio-lateral position of axons through robo2 and robo3, and restoring robo3 expression in hb9 mutants rescues the lateral position defects of a subset of neurons. Altogether, these data identify Robo2 and Robo3 as key effectors of Hb9 in regulating nervous system development.
Keywords	Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2014-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article: A novel C. elegans zinc finger transcription factor, lsy-2, required for the cell type-specific expression of the lsy-6 microRNA.

Johnston, Robert J / Hobert, Oliver

Development (Cambridge, England)

2005 Volume 132, Issue 24, Page(s) 5451–5460

Abstract: ... in ASEL for the activation of ASEL-specifying factors and the repression of ASER-specifying factors ... morphologically bilaterally symmetric, yet left/right asymmetric in function and in the expression of specific ... gene regulatory network composed of microRNAs (miRNAs) and transcription factors. Alterations in the activities ...

Abstract	The two Caenorhabditis elegans gustatory neurons, ASE left (ASEL) and ASE right (ASER) are morphologically bilaterally symmetric, yet left/right asymmetric in function and in the expression of specific chemosensory signaling molecules. The ASEL versus ASER cell-fate decision is controlled by a complex gene regulatory network composed of microRNAs (miRNAs) and transcription factors. Alterations in the activities of each of these regulatory factors cause a complete lateral cell-fate switch. Here, we describe lsy-2, a novel C2H2 zinc finger transcription factor that is required for the execution of the ASEL stable state. In lsy-2 null mutants, the ASEL neuron adopts the complete ASER gene expression profile, including both upstream regulatory and terminal effector genes. The normally left/right asymmetric ASE neurons are therefore ;symmetrized' in lsy-2 mutants. Cell-specific rescue experiments indicate that lsy-2 is required autonomously in ASEL for the activation of ASEL-specifying factors and the repression of ASER-specifying factors. Genetic epistasis experiments demonstrate that lsy-2 exerts its activity by regulating the transcription of the lsy-6 miRNA in the ASEL neuron, thereby making lsy-2 one of the few factors known to control the cell-type specificity of miRNA gene expression.
MeSH term(s)	Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Body Patterning/physiology ; Caenorhabditis elegans/cytology ; Caenorhabditis elegans/growth & development ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/biosynthesis ; Caenorhabditis elegans Proteins/genetics ; Epistasis, Genetic ; Gene Regulatory Networks ; MicroRNAs/biosynthesis ; MicroRNAs/genetics ; Molecular Sequence Data ; Mutation ; Neurons/cytology ; Neurons/physiology ; Transcription Factors/biosynthesis ; Transcription Factors/genetics ; Zinc Fingers
Chemical Substances	Caenorhabditis elegans Proteins ; Lsy-2 protein, C elegans ; MicroRNAs ; Transcription Factors
Language	English
Publishing date	2005-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.02163
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Article: PACAP and NGF regulate common and distinct traits of the sympathoadrenal lineage: effects on electrical properties, gene markers and transcription factors in differentiating PC12 cells.

Grumolato, Luca / Louiset, Estelle / Alexandre, David / Aït-Ali, Djida / Turquier, Valérie / Fournier, Alain / Fasolo, Aldo / Vaudry, Hubert / Anouar, Youssef

The European journal of neuroscience

2003 Volume 17, Issue 1, Page(s) 71–82

Abstract: ... of neuronal and neuroendocrine marker genes, and activity of transcription factors during differentiation ... instrumental for sympathoadrenal development. To compare downstream effectors activated by PACAP and NGF ... these results show that PACAP and NGF exert common as well as different effects on neuronal and neuroendocrine ...

Abstract	To determine the possible role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the development of the sympathoadrenal cell lineage, we have examined the effects of this neurotrophic peptide, in comparison to nerve growth factor (NGF), on the morphology, electrophysiological properties, expression of neuronal and neuroendocrine marker genes, and activity of transcription factors during differentiation of sympathoadrenal-derived cells, using the rat pheochromocytoma PC12 cell model. Both PACAP and NGF elicited rapid neurite outgrowth, which was accompanied by induction of cell excitability and the development of both sodium and calcium currents. Concurrently, PACAP and NGF increased the expression of a marker of synaptic vesicles. By contrast, PACAP, but not NGF, regulated the expression of different constituents of neuroendocrine large dense core vesicles in PC12 cells. Furthermore, PACAP and NGF differentially regulated the expression of mammalian achaete-scute homologue and paired homeobox 2b genes, transcription factors instrumental for sympathoadrenal development. To compare downstream effectors activated by PACAP and NGF, we studied the effects of these factors on the binding activity of consensus 12-O-tetradecanoylphorbol-13-acetate- and cAMP-responsive elements to nuclear extracts of differentiating PC12 cells. We found that both PACAP and NGF markedly increase the binding activity of these cis-regulatory sequences and that PACAP preferentially recruits activator protein-1-like transcription factors to these elements. Taken together, these results show that PACAP and NGF exert common as well as different effects on neuronal and neuroendocrine traits in differentiating PC12 cells, strongly suggesting that these two trophic factors could play complementary roles in the development of the sympathoadrenal cell lineage.
MeSH term(s)	Adrenal Glands/drug effects ; Adrenal Glands/metabolism ; Animals ; Blotting, Northern ; Blotting, Western ; Calcium Channels/drug effects ; Calcium Channels/metabolism ; Carrier Proteins/drug effects ; Carrier Proteins/metabolism ; Cell Culture Techniques ; Cell Differentiation/drug effects ; Electrophysiology ; Gene Expression Regulation ; Genes, Homeobox/drug effects ; Membrane Glycoproteins/drug effects ; Membrane Glycoproteins/metabolism ; Membrane Transport Proteins ; Nerve Growth Factor/metabolism ; Nerve Growth Factor/pharmacology ; Nerve Growth Factors/metabolism ; Nerve Growth Factors/pharmacology ; Neuropeptides/metabolism ; Neuropeptides/pharmacology ; PC12 Cells ; Pituitary Adenylate Cyclase-Activating Polypeptide ; RNA, Messenger/metabolism ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Sodium Channels/drug effects ; Sodium Channels/metabolism ; Sympathetic Nervous System/drug effects ; Sympathetic Nervous System/metabolism ; Sympathetic Nervous System/physiology ; Synaptic Vesicles/drug effects ; Synaptic Vesicles/metabolism ; Transcription Factors/drug effects ; Transcription Factors/metabolism ; Vesicular Acetylcholine Transport Proteins ; Vesicular Biogenic Amine Transport Proteins ; Vesicular Transport Proteins
Chemical Substances	Adcyap1 protein, rat ; Calcium Channels ; Carrier Proteins ; Membrane Glycoproteins ; Membrane Transport Proteins ; Nerve Growth Factors ; Neuropeptides ; Pituitary Adenylate Cyclase-Activating Polypeptide ; RNA, Messenger ; Slc18a3 protein, rat ; Sodium Channels ; Transcription Factors ; Vesicular Acetylcholine Transport Proteins ; Vesicular Biogenic Amine Transport Proteins ; Vesicular Transport Proteins ; Nerve Growth Factor (9061-61-4)
Language	English
Publishing date	2003-01
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1046/j.1460-9568.2003.02426.x
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Article ; Online: Sensory neuron fates are distinguished by a transcriptional switch that regulates dendrite branch stabilization.

Smith, Cody J / O'Brien, Timothy / Chatzigeorgiou, Marios / Spencer, W Clay / Feingold-Link, Elana / Husson, Steven J / Hori, Sayaka / Mitani, Shohei / Gottschalk, Alexander / Schafer, William R / Miller, David M

Neuron

2013 Volume 79, Issue 2, Page(s) 266–280

Abstract: ... to specific stimuli. Transcription factors and their downstream effectors orchestrate this outcome but are ... with the simple morphology of AVM and PVM touch neurons. AHR-1 specifies AVM touch neuron fate by elevating MEC-3 ... Sensory neurons adopt distinct morphologies and functional modalities to mediate responses ...

Abstract	Sensory neurons adopt distinct morphologies and functional modalities to mediate responses to specific stimuli. Transcription factors and their downstream effectors orchestrate this outcome but are incompletely defined. Here, we show that different classes of mechanosensory neurons in C. elegans are distinguished by the combined action of the transcription factors MEC-3, AHR-1, and ZAG-1. Low levels of MEC-3 specify the elaborate branching pattern of PVD nociceptors, whereas high MEC-3 is correlated with the simple morphology of AVM and PVM touch neurons. AHR-1 specifies AVM touch neuron fate by elevating MEC-3 while simultaneously blocking expression of nociceptive genes such as the MEC-3 target, the claudin-like membrane protein HPO-30, that promotes the complex dendritic branching pattern of PVD. ZAG-1 exercises a parallel role to prevent PVM from adopting the PVD fate. The conserved dendritic branching function of the Drosophila AHR-1 homolog, Spineless, argues for similar pathways in mammals.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Caenorhabditis elegans ; Dendrites/physiology ; Dendritic Spines/physiology ; Neurogenesis/physiology ; Sensory Receptor Cells/physiology ; Transcription Factors/physiology ; Transcription, Genetic/physiology
Chemical Substances	Transcription Factors
Language	English
Publishing date	2013-04-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2013.05.009
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