POU Domain Factors in the Neuroendocrine System: Lessons from Developmental Biology Provide Insights into Human Disease*

Andersen, Bogi; Rosenfeld, Michael G.

doi:10.1210/edrv.22.1.0421

Cited by 118 publications

(107 citation statements)

References 418 publications

(228 reference statements)

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“…Members of the POU family have been shown to influence the neuroendocrine system during puberty and early development of vertebrates [7]–[13]. POU proteins have a highly conserved POU homeodomain and regulate gene expression by binding to high-affinity octamer sites [8], [14].…”

Section: Introductionmentioning

confidence: 99%

The POU Factor Ventral Veins Lacking/Drifter Directs the Timing of Metamorphosis through Ecdysteroid and Juvenile Hormone Signaling

Cheng

Chaieb

et al. 2014

PLoS Genet

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Although endocrine changes are known to modulate the timing of major developmental transitions, the genetic mechanisms underlying these changes remain poorly understood. In insects, two developmental hormones, juvenile hormone (JH) and ecdysteroids, are coordinated with each other to induce developmental changes associated with metamorphosis. However, the regulation underlying the coordination of JH and ecdysteroid synthesis remains elusive. Here, we examined the function of a homolog of the vertebrate POU domain protein, Ventral veins lacking (Vvl)/Drifter, in regulating both of these hormonal pathways in the red flour beetle, Tribolium castaneum (Tenebrionidae). RNA interference-mediated silencing of vvl expression led to both precocious metamorphosis and inhibition of molting in the larva. Ectopic application of a JH analog on vvl knockdown larvae delayed the onset of metamorphosis and led to a prolonged larval stage, indicating that Vvl acts upstream of JH signaling. Accordingly, vvl knockdown also reduced the expression of a JH biosynthesis gene, JH acid methyltransferase 3 (jhamt3). In addition, ecdysone titer and the expression of the ecdysone response gene, hormone receptor 3 (HR3), were reduced in vvl knockdown larvae. The expression of the ecdysone biosynthesis gene phantom (phm) and spook (spo) were reduced in vvl knockdown larvae in the anterior and posterior halves, respectively, indicating that Vvl might influence ecdysone biosynthesis in both the prothoracic gland and additional endocrine sources. Injection of 20-hydroxyecdysone (20E) into vvl knockdown larvae could restore the expression of HR3 although molting was never restored. These findings suggest that Vvl coordinates both JH and ecdysteroid biosynthesis as well as molting behavior to influence molting and the timing of metamorphosis. Thus, in both vertebrates and insects, POU factors modulate the production of major neuroendocrine regulators during sexual maturation.

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Section: Introductionmentioning

confidence: 99%

The POU Factor Ventral Veins Lacking/Drifter Directs the Timing of Metamorphosis through Ecdysteroid and Juvenile Hormone Signaling

Cheng

Chaieb

et al. 2014

PLoS Genet

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“…POU4F3 is a member of the POU family of transcription factors that regulate a wide array of neuroendocrine developmental pathways [1]. This family is characterised by the presence of a bipartite DNA binding domain known as the POU domain which comprises a POU-homeodomain and a POU-specific domain separated by a linker [2].…”

Section: Introductionmentioning

confidence: 99%

Regulation of the Orphan Nuclear Receptor Nr2f2 by the DFNA15 Deafness Gene Pou4f3

et al. 2014

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Hair cells are the mechanotransducing cells of the inner ear that are essential for hearing and balance. POU4F3 – a POU-domain transcription factor selectively expressed by these cells – has been shown to be essential for hair cell differentiation and survival in mice and its mutation in humans underlies late-onset progressive hearing loss (DFNA15). The downstream targets of POU4F3 are required for hair cell differentiation and survival. We aimed to identify such targets in order to elucidate the molecular pathways involved in hair cell production and maintenance. The orphan thyroid nuclear receptor Nr2f2 was identified as a POU4F3 target using a subtractive hybridization strategy and EMSA analysis showed that POU4F3 binds to two sites in the Nr2f2 5′ flanking region. These sites were shown to be required for POU4F3 activation as their mutation leads to a reduction in the response of an Nr2f2 5′ flanking region reporter construct to POU4F3. Immunocytochemistry was carried out in the developing and adult inner ear in order to investigate the relevance of this interaction in hearing. NR2F2 expression in the postnatal mouse organ of Corti was shown to be detectable in all sensory epithelia examined and characterised. These data demonstrate that Nr2f2 is a direct target of POU4F3 in vitro and that this regulatory relationship may be relevant to hair cell development and survival.

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“…This domain is composed of a classic homeodomain and a highly conserved POU-specific domain of 76-78 amino acids. These two major subdomains are joined together by a short linker region with variable length and sequence [1][2][3]. The POU domain contributes both to site-specific DNA-binding and to interactions between POU domain proteins and other transcription factors [4].…”

Section: Introductionmentioning

confidence: 99%

“…Experimental and genetic studies have revealed the crucial role of POU family factors in development of multiple tissues, especially in the nervous system [5][6][7][8]. Based upon amino acid sequence similarities of the POU domain, POU genes can be grouped into at least six classes [3,9].…”

Section: Introductionmentioning

confidence: 99%

Expression and Antibody Preparation of POU Transcription Factor qBrn-1

Ling¹,

Liu²,

Liu³

et al. 2007

PPL

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Abstract:The transcription factor Brn-1, which belongs to POU-domain family, has been shown to play critical roles in the development of the nervous system. A cDNA clone coding for a quail Brn-1 homologue, qBrn-1, was isolated. To investigate whether this gene plays a role in the development of the quail nervous system, an anti-N-terminal peptide antibody was prepared. The coding region for amino acids 1-79 (the N-terminal domain of qBrn-1) was subcloned into Trx fusion expression vector pET32c and introduced into the Escherichia coli Origami(DE3) cells for efficient expression. After purification, Trx-fused polypeptides, called Trx-qBrn-1N, were used to immunize the rabbits to prepare polyclonal antibodies against qBrn-1. The produced and purified antiserum showed specificity not only to the in vitro expressed qBrn-1, but also to the natural qBrn-1 in tissues. Immunolabeling on sections by the anti-qBrn-1 serum showed that qBrn-1 was specifically expressed in the developing spinal cord and kidney. This suggests that qBrn-1 may play some roles in the development of avian nervous system and kidney, and the preparation of anti-qBrn-1 polyclonal antibody will facilitate further detection of, and functional study on, qBrn-1 both in vivo and in vitro.

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POU Domain Factors in the Neuroendocrine System: Lessons from Developmental Biology Provide Insights into Human Disease*

Cited by 118 publications

References 418 publications

The POU Factor Ventral Veins Lacking/Drifter Directs the Timing of Metamorphosis through Ecdysteroid and Juvenile Hormone Signaling

The POU Factor Ventral Veins Lacking/Drifter Directs the Timing of Metamorphosis through Ecdysteroid and Juvenile Hormone Signaling

Regulation of the Orphan Nuclear Receptor Nr2f2 by the DFNA15 Deafness Gene Pou4f3

Expression and Antibody Preparation of POU Transcription Factor qBrn-1

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