Noradrenergic neurons in the zebrafish hindbrain are induced by retinoic acid and require<i>tfap2a</i>for expression of the neurotransmitter phenotype

Holzschuh, Jochen; Barrallo-Gimeno, Alejandro; Ettl, Anne-Kathrin; Dürr, Katrin; Knapik, Ela W.; Driever, Wolfgang

doi:10.1242/dev.00816

Cited by 105 publications

(106 citation statements)

References 77 publications

(85 reference statements)

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“…AP-2␤, a member of the AP-2 family of retinoic acid-induced transcription factors was highly enriched in LC neurons. The closely related transcription factor AP-2␣, which recognizes the same target sequence and shares a highly conserved DNA-binding and dimerization domain with AP-2␤, has been shown to activate the expression of TH and DBH (23) and to be essential for the development of NA LC neurons in zebrafish (24). We also observed high specific expression of potential vulnerability factors, the Cu transporter 1, the ␥-glutamyltranspeptidase-related enzyme, and prostaglandin E synthase.…”

Section: Resultsmentioning

confidence: 66%

Molecular basis for catecholaminergic neuron diversity

Grimm

Mueller

Hefti

et al. 2004

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

131

140

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Catecholaminergic neurons control diverse cognitive, motor, and endocrine functions and are associated with multiple psychiatric and neurodegenerative disorders. We present global gene-expression profiles that define the four major classes of dopaminergic (DA) and noradrenergic neurons in the brain. Hypothalamic DA neurons and noradrenergic neurons in the locus coeruleus display distinct group-specific signatures of transporters, channels, transcription, plasticity, axon-guidance, and survival factors. In contrast, the transcriptomes of midbrain DA neurons of the substantia nigra and the ventral tegmental area are closely related with <1% of differentially expressed genes. Transcripts implicated in neural plasticity and survival are enriched in ventral tegmental area neurons, consistent with their role in schizophrenia and addiction and their decreased vulnerability in Parkinson's disease. The molecular profiles presented provide a basis for understanding the common and population-specific properties of catecholaminergic neurons and will facilitate the development of selective drugs.C atecholaminergic (CA) neurons producing the neurotransmitters dopamine (DA) and noradrenalin (NA) are organized in anatomically discrete groups and constitute Ϸ1 of 10 7 cells in the vertebrate CNS (1, 2). The most prominent groups of DA neurons reside in the substantia nigra (SN; A9 cell group; Ϸ10,000 neurons in the rat) and the ventral tegmental area (VTA; A10; Ϸ25,000 neurons) of the midbrain. The SN neurons provide the nigrostriatal ascending inputs to the telencephalon and comprise a key component of the extrapyramidal motor system controlling postural reflexes and initiation of movement. DA neurons in the adjacent VTA give rise to mesocortical and mesolimbic pathways that are implicated in control of emotional balance, reward-associated behavior, attention, and memory. Additional groups of DA neurons reside in the medial zona incerta of the hypothalamus (A13; Ϸ900 neurons) and participate in the regulation of endocrine functions. The largest collection of NA neurons resides in the pontine locus coeruleus (LC; Ϸ1,500 neurons). These neurons form a modulatory projection system to most CNS areas and contribute to the regulation of emotional status, sensory perception, arousal, sleepwake patterns, and most autonomic functions.Consistent with their varied functions, the CA neurons are associated with multiple neurodegenerative, psychiatric, and endocrine disorders. Selective degeneration of DA neurons in the SN but not in the VTA or the hypothalamus leads to Parkinson's disease (PD) (3-7), whereas abnormal function of the VTA DA neurons has been linked to schizophrenia, attention deficit, addiction, and hyperactivity disorders (8-11). In addition, dysfunction of hypothalamic DA neurons can cause hyperprolactinemia, an endocrine disorder of the reproductive system (12), whereas changes in the activity of the NA system have been linked to depression as well as sleep disorders (13,14).The drugs currently available for therapy reflec...

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Section: Resultsmentioning

confidence: 66%

Molecular basis for catecholaminergic neuron diversity

Grimm

Mueller

Hefti

et al. 2004

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

131

140

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“…To avoid formation of melanin pigments, embryos were incubated in 0.2 mM 1-phenyl-2 thiourea (Sigma). mcm5 m850 was isolated during an ethyl-nitrosourea mutagenesis screen performed in our laboratory (15).…”

Section: Methodsmentioning

confidence: 99%

Depletion of minichromosome maintenance protein 5 in the zebrafish retina causes cell-cycle defect and apoptosis

Ryu

Holzschuh

Erhardt

et al. 2005

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

Self Cite

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In multicellular organisms, the control of genome duplication and cell division must be tightly coordinated. Essential roles of the minichromosome maintenance (MCM) proteins for genome duplication have been well established. However, no genetic model has been available to address the function of MCM proteins in the context of vertebrate organogenesis. Here, we present positional cloning of a zebrafish mcm5 mutation and characterization of its retina phenotype. In the retina, mcm5 expression correlates closely with the pattern of cell proliferation. By the third day of development, mcm5 is down-regulated in differentiated cells but is maintained in regions containing retinal stem cells. We demonstrate that a gradual depletion of maternally derived MCM5 protein leads to a prolonged S phase, cell-cycle-exit failure, apoptosis, and reduction in cell number in mcm5 m850 mutant embryos. Interestingly, by the third day of development, increased apoptosis is detectable only in the retina, tectum, and hindbrain but not in other late-proliferating tissues, suggesting that different tissues may employ distinct cellular programs in responding to the depletion of MCM5.stem cell ͉ cell proliferation ͉ ciliary marginal zone ͉ embryogenesis ͉ development P roper duplication of the genome during the cell cycle is of paramount importance for the life of an organism. In eukaryotes, each replication origin is ''licensed'' to fire once per cell cycle through the cell-cycle-dependent formation and destruction of a prereplication complex (preRC) (1-3). A key component of this preRC is a family of six structurally related proteins, MCM2 through -7, which are evolutionarily conserved in all eukaryotes. The MCM proteins were originally identified as proteins required for minichromosome maintenance in Saccharomyces cerevisiae (4). MCM2 through -7 belong to a distinct subgroup of the large AAAϩ ATPase family (5) and share a conserved central region of Ϸ200 amino acids (MCM box). Biochemical studies in Xenopus have established the role of MCM2 through -7 as replication-licensing factors (6-8). Subsequent studies illustrate that proper orchestration of the functional interactions among MCM2 through -7 proteins and other components of the preRC by cell-cycledependent protein kinases results in initiation of DNA synthesis once every cell cycle (9, 10). The MCM2 through -7 proteins appear to form heterohexamers and play important roles in initiation and elongation during DNA replication (4,11,12). Furthermore, recent evidence supports involvement of MCMs in many other chromosome transactions, including transcription, chromatin remodeling, and genome stability (13). However, in vivo analysis of MCMprotein functions in multicellular organism has been scarce. Here, we report the isolation, positional cloning, and in-depth characterization of a vertebrate mutant in an MCM-family protein. We demonstrate that the zebrafish m850 allele harbors a mutation in the mcm5 gene and exhibits developmental defects in lateproliferating tissues, including the re...

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“…The human gene encoding AP-2␣, TFAP2A, maps in close proximity to a region of chromosome 6p24 that is frequently involved in translocations and deletions associated with orofacial clefting (Davies et al, 1999a(Davies et al, ,b, 2004Topping et al, 2002;Schultz et al, 2004), raising the possibility that alterations in the long-range cis-regulatory sequences controlling TFAP2A expression might be responsible for congenital defects affecting human facial development. In the context of evolution, evidence from multiple species indicates that changes in the spatial and temporal regulation of the AP-2 family of genes, among others, might underlie the evolution of the vertebrate neural crest and, ultimately, the diversity of craniofacial skeleton (Meulemans and BronnerFraser, 2002;Holzschuh et al, 2003;Knight et al, 2003Knight et al, , 2005Luo et al, 2003;O'Brien et al, 2004). To identify the regulatory hierarchy underlying the expression of Tcfap2a, and to determine how it might have been altered during evolution, or in human genetic disease, we have previously analyzed various species to locate regions of the gene that are responsible for driving AP-2␣ expression in different tissues (Zhang and Williams, 2003;Zhang et al, unpublished data).…”

Section: Regulation Of Tcfap2a In the Fnp And Lbm Are Controlled By Dmentioning

confidence: 99%

Frontal nasal prominence expression driven by Tcfap2a relies on a conserved binding site for STAT proteins

Donner

Williams

2006

Developmental Dynamics

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The AP-2 transcription factor family is linked with development of the head and limbs in both vertebrate and invertebrate species. Recent evidence has also implicated this gene family in the evolution of the neural crest in chordates, a critical step that allowed the development and elaboration of the vertebrate craniofacial skeleton. In mice, the inappropriate embryonic expression of one particular AP-2 gene, Tcfap2a, encoding AP-2␣, results in multiple developmental abnormalities, including craniofacial and limb defects. Thus, Tcfap2a provides a valuable genetic resource to analyze the regulatory hierarchy responsible for the evolution and development of the face and limbs. Previous studies have identified a 2-kilobase intronic region of both the mouse and human AP-2␣ locus that directs expression of a linked LacZ transgene to the facial processes and the distal mesenchyme of the limb bud in transgenic mice. Further analysis identified two highly conserved regions of ϳ200 -400 bp within this tissue-specific enhancer. We have now initiated a transgenic and biochemical analysis of the most important of these highly conserved regions. Our analysis indicates that although the sequences regulating face and limb expression have been integrated into a single enhancer, different cis-acting sequences ultimately control these two expression domains. Moreover, these studies demonstrate that a conserved STAT binding site provides a major contribution to the expression of Tcfap2a in the facial prominences. Developmental Dynamics 235: 1358 -1370, 2006.

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Noradrenergic neurons in the zebrafish hindbrain are induced by retinoic acid and requiretfap2afor expression of the neurotransmitter phenotype

Abstract: SummaryNoradrenergic neurons in the zebrafish hindbrain are induced by retinoic acid and require tfap2a for expression of the neurotransmitter phenotype

Cited by 105 publications

References 77 publications

Molecular basis for catecholaminergic neuron diversity

Molecular basis for catecholaminergic neuron diversity

Depletion of minichromosome maintenance protein 5 in the zebrafish retina causes cell-cycle defect and apoptosis

Frontal nasal prominence expression driven by Tcfap2a relies on a conserved binding site for STAT proteins

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