Molecular control of ciliary neuron development: BMPs and downstream transcriptional control in the parasympathetic lineage

Müller, Frank; Rohrer, Hermann

doi:10.1242/dev.00165

Cited by 71 publications

(88 citation statements)

References 70 publications

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“…In this work, we have investigated the interactions between two noradrenergic transcription factors, dHAND and Arix, at the DBH promoter proximal region. Previous work has shown the importance of dHAND in the development and maintenance of the noradrenergic phenotype (13,15,16); but until now, there has been no evidence that dHAND directly interacts with the noradrenergic biosynthetic gene regulatory regions. In this study, we have demonstrated that dHAND and Arix cooperate to activate transcription of the DBH promoter and that the dHAND-Arix complex contacts the DNA through the HD sites.…”

Section: Discussionmentioning

confidence: 99%

“…In vivo, this interaction between Arix and dHAND could enhance the selectivity of Arix for the appropriate HD sites. In developing autonomic neurons, only cells containing both dHAND and Phox2 (Arix) proteins express noradrenergic traits (16), and this tripartite Arix-dHAND-DNA interaction could be the basis for the noradrenergic phenotype.…”

Section: Dhand Interacts Independent Of Dna Bindingmentioning

confidence: 99%

“…dHAND is required for cardiac (7), vascular (10), and craniofacial development (11) and is an important factor in limb (12) and sympathetic neuron (13,14) development. Recent evidence has demonstrated that the expression of genes that lead to norepinephrine production can be elicited by ectopic dHAND expression in avian embryos (15,16).Several of the class II bHLH proteins have been shown to associate with other transcription factors. For example, NeuroD1-E47 interacts with Pitx1, a homeodomain (HD) protein, to regulate expression of the pituitary pro-opiomelanocortin gene (17), and this interaction is dependent on both transcription factors binding to the promoter.…”

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The Interaction between dHAND and Arix at the Dopamine β-Hydroxylase Promoter Region Is Independent of Direct dHAND Binding to DNA

Rychlik

Gerbasi

Lewis

2003

Journal of Biological Chemistry

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Dopamine ␤-hydroxylase (DBH) catalyzes the production of norepinephrine, and its expression defines the noradrenergic phenotype. Transcription factors dHAND, a basic helix-loop-helix protein, and Arix/ Phox2a, a homeoprotein, have been demonstrated to play a role in the differentiation and maintenance of catecholaminergic neurons. Three Arix regulatory sites have been identified in the DBH promoter proximal region, but there is no such evidence for dHAND. Cotransfection with a DBH promoter-luciferase reporter construct plus dHAND or dHAND-E12 expression plasmids did not alter luciferase activity, whereas transfection with Arix resulted in a 2.5-fold stimulation of luciferase activity. However, a 5.5-fold increase was observed when Arix and dHAND were combined, and an 8-fold level of expression was observed when Arix was transfected with a dHAND mutant lacking the basic DNAbinding domain. When the homeodomain sites in the DBH promoter proximal region were mutated, all activity was lost, demonstrating dependence upon Arix-DNA interaction for transcriptional activation. In electrophoretic mobility shift assays, the addition of dHAND decreased the amount of Arix needed to elicit a mobility shift with the DBH homeodomain sites, and the dHAND basic mutant potentiated Arix binding in a manner similar to wild-type dHAND. The dHAND-Arix complex was dissociated upon the addition of an unlabeled competitor containing a homeodomain, but not upon the addition of a competitor containing E-boxes. Arix coprecipitated with antisera directed against recombinant dHAND, demonstrating direct protein-protein interactions. These results indicate that the activation of the DBH promoter by Arix is potentiated by dHAND via a mechanism independent of a direct interaction of dHAND with DNA.Cell-specific transcription is accomplished by the precise and transient interactions of numerous and complex molecular factors. Basic helix-loop-helix (bHLH) 1 proteins are transcription factors that play an important role in the development and differentiation of specific cell types such as neurons (1), appendages (2), and myocytes (3, 4). These bHLH proteins have been shown to bind to defined consensus sites, E-boxes (CANNTG), through the basic domain and require dimerization partners (via helices) to activate transcription. These proteins have been divided into several classes based on structure, function, and tissue specificity. Class I bHLH proteins (E12 and E47) are expressed ubiquitously in all tissues and can function as homodimers, but prefer to form heterodimers with other bHLH proteins (5). Class II proteins (dHAND, NeuroD, and MyoD) are expressed in specific tissues and are believed to be functionally active when complexed with a class I protein (5, 6). dHAND/HAND2 (deciduum, heart, autonomic nervous system, and neural crest cell derivatives) is a 30-kDa member of the class II bHLH protein family (7,8) and has been detected in Xenopus, zebrafish, chicks, mice, and humans (9). dHAND is required for cardiac (7), vascular (10), and craniofacial...

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Section: Discussionmentioning

confidence: 99%

Section: Dhand Interacts Independent Of Dna Bindingmentioning

confidence: 99%

mentioning

confidence: 99%

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The Interaction between dHAND and Arix at the Dopamine β-Hydroxylase Promoter Region Is Independent of Direct dHAND Binding to DNA

Rychlik

Gerbasi

Lewis

2003

Journal of Biological Chemistry

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“…Although neuronal migration is common in the developing CNS, there is currently little evidence about whether developing peripheral neurons can migrate. In developing parasympathetic, sympathetic and dorsal root ganglia, the neural crest-derived precursors arrive at their final destination before differentiating into neurons (Schneider et al, 1999;Muller and Rohrer, 2002).…”

Section: Introductionmentioning

confidence: 99%

The migratory behavior of immature enteric neurons

Hao

Anderson

Kobayashi

et al. 2008

Developmental Neurobiology

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While they are migrating caudally along the developing gut, around 10%-20% of enteric neural crest-derived cells start to express pan-neuronal markers and tyrosine hydroxylase (TH). We used explants of gut from embryonic TH-green fluorescence protein (GFP) mice and time-lapse microscopy to examine whether these immature enteric neurons migrate and their mode of migration. In the gut of E10.5 and E11.5 TH-GFP mice, around 50% of immature enteric neurons (GFP + cells) migrated, with an average speed of around 15 lm/h. This is slower than the speed at which the population of enteric neural crest-derived cells advances along the developing gut, and hence neuronal differentiation seems to slow, but not necessarily halt, the caudal migration of enteric neural crest cells. Most migrating immature enteric neurons migrated caudally by extending a long-leading process followed by translocation of the cell body. This mode of migration is different from that of non-neuronal enteric neural crestderived cells and neural crest cells in other locations, but resembles that of migrating neurons in many regions of the developing central nervous system (CNS). In migrating immature enteric neurons, a swelling often preceded the movement of the nucleus in the direction of the leading process. However, the centrosomal marker, pericentrin, was not localized to either the leading process or swelling. This seems to be the first detailed report of neuronal migration in the developing mammalian peripheral nervous system. ' 2008 Wiley Periodicals, Inc. Develop Neurobiol 69: 22-35, 2009

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