Sim2 Contributes to Neuroendocrine Hormone Gene Expression in the Anterior Hypothalamus

Goshu, Eleni; Jin, Hui; Lovejoy, John F.; Marion, Jean-François; Michaud, Jacques L.; Fan, Chen‐Ming

doi:10.1210/me.2003-0372

Cited by 63 publications

(64 citation statements)

References 39 publications

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“…In mice, two SIM genes, Sim1 and Sim2, are expressed in overlapping patterns in the hypothalamus and are both expressed in the HNS, although gene knockout experiments demonstrate that only Sim1 is required for oxytocin cell development (Michaud et al, 1998;Goshu et al, 2002;Goshu et al, 2004). Sequence comparisons show that zebrafish sim1 is most similar to mouse/human Sim1/SIM1, while zebrafish sim2 is most similar to mouse/human Sim2/SIM2.…”

Section: Discussionmentioning

confidence: 99%

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The zebrafish bHLH PAS transcriptional regulator, single‐minded 1 (sim1), is required for isotocin cell development

Eaton

Glasgow

2006

Developmental Dynamics

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A wide range of physiological and behavioral processes, such as social, sexual, and maternal behaviors, learning and memory, and osmotic homeostasis are influenced by the neurohypophysial peptides oxytocin and vasopressin. Disruptions of these hormone systems have been linked to several neurobehavioral disorders, including autism, Prader-Willi syndrome, affective disorders, and obsessive-compulsive disorder. Studies in zebrafish promise to reveal the complex network of regulatory genes and signaling pathways that direct the development of oxytocin-and vasopressin-like neurons, and provide insight into factors involved in brain disorders associated with disruption of these systems. Isotocin, which is homologous to oxytocin, is expressed early, in a simple pattern in the developing zebrafish brain. Single-minded 1 (sim1), a member of the bHLH-PAS family of transcriptional regulatory genes, is required for terminal differentiation of mammalian oxytocin cells and is a master regulator of neurogenesis in Drosophila. Here we show that sim1 is expressed in the zebrafish forebrain and is required for isotocin cell development. The expression pattern of sim1 mRNA in the embryonic forebrain is dynamic and complex, and overlaps with isotocin expression in the preoptic area. We provide evidence that the role of sim1 in zebrafish neuroendocrine cell development is evolutionarily conserved with that of mammals.

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Section: Discussionmentioning

confidence: 99%

“…In mammals, there is also a second sim gene, Sim2, which is expressed in the hypothalamus, yet has no role in oxytocin cell development. It is, however, required for TRH and SS cellular development in the aPV and PVN where this function is dependent upon Sim1 (Goshu et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

The zebrafish bHLH PAS transcriptional regulator, single‐minded 1 (sim1), is required for isotocin cell development

Eaton

Glasgow

2006

Developmental Dynamics

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“…The presence of TRH throughout the central nervous system as well as in numerous peripheral organs supports a diverse range of roles for this molecule outside of the traditional HPT axis, including a potential role as a neurotransmitter. During mouse embryogenesis, Trh mRNA has been detected in the neural folds at E8.0, at the midbrain-hindbrain junction from E8.5 to E10.5, and in the developing hypothalamus from E11.5 to E18.5 (Schonemann et al, 1995;Michaud et al, 1998Michaud et al, , 2000Acampora et al, 1999;Wang and Lufkin, 2000;Keith et al, 2001;Backman et al, 2003;Goshu et al, 2004;Caqueret et al, 2006;Jukkola et al, 2006). Despite the critical role of TRH in regulating the HPT axis and its expression in developing neural structures, mice deficient in Trh are viable and fertile (Yamada et al, 1997(Yamada et al, , 2003.…”

Section: Introductionmentioning

confidence: 99%

Dynamic expression of Thyrotropin‐releasing hormone in the mouse definitive endoderm

McKnight¹,

Hou²,

Hoodless³

2007

Developmental Dynamics

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Thyrotropin-releasing hormone (TRH) is a well-characterized regulator of the hypothalamic-pituitary-thyroid endocrine axis. Here, we describe the expression of Trh during early embryonic development in the mouse. We find Trh to be highly expressed during postimplantation stages in the mouse embryo, with expression first observed in the epiblast at embryonic day (E) 6.5. During gastrulation, Trh is expressed in the newly formed definitive endoderm cells, and at embryonic day (E) 7.75, marks the entire definitive endoderm. Subsequently, Trh mRNA levels rapidly decrease such that, by E9.0, expression in the definitive endoderm is no longer detected, after which neural expression predominates. Thus, Trh is expressed dynamically and specifically in the developing mouse definitive endoderm from E7.0 to E8.5. Trh is unique among definitive endoderm markers as it transiently marks the entire definitive endoderm population and is not expressed in the extraembryonic endoderm. Trh will be a valuable tool to study definitive endoderm formation in the mouse embryo.

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“…We have generated, by homologous recombination, a null allele of Sim1 (Sim1 The bHLH-PAS transcription factors SIM1 and SIM2 are closely related paralogues, the expression profiles of which overlap in regions of the anterior hypothalamus that will give rise to the paraventricular (PVN), supraoptic (SON) and anterior periventricular (APV) nuclei (Fan et al, 1996). Sim1 is required for the differentiation of virtually all neurons of the PVN/SON/APV, whereas Sim2 controls the differentiation of a subset of PVN and APV neurons (Michaud et al, 1998;Goshu et al, 2004). The interplay between Sim1 and Sim2 is complex; mutant analysis indicates that Sim1 acts upstream of Sim2, but can also compensate for the lack of Sim2, albeit ineffectively.…”

Section: Introductionmentioning

confidence: 99%

Sim1andSim2are required for the correct targeting of mammillary body axons

et al. 2005

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The mammillary body (MB), and its axonal projections to the thalamus(mammillothalamic tract, MTT) and the tegmentum (mammillotegmental tract,MTEG), are components of a circuit involved in spatial learning. The bHLH-PAS transcription factors SIM1 and SIM2 are co-expressed in the developing MB. We have found that MB neurons are generated and that they survive at least until E18.5 in embryos lacking both Sim1 and Sim2(Sim1-/-;Sim2-/-). However, the MTT and MTEG are histologically absent in Sim1-/-;Sim2-/- embryos, and are reduced in embryos lacking Sim1 but bearing one or two copies of Sim2, indicating a contribution of the latter to the development of MB axons. We have generated, by homologous recombination, a null allele of Sim1 (Sim1tlz) in which the tau-lacZfusion gene was introduced, allowing the staining of MB axons. Consistent with the histological studies, lacZ staining showed that the MTT/MTEG is barely detectable in Sim1tlz/tlz;Sim2+/- and Sim1tlz/tlz;Sim2-/- brains. Instead, MB axons are splayed and grow towards the midline. Slit1 and Slit2,which code for secreted molecules that induce the repulsion of ROBO1-producing axons, are expressed in the midline at the level of the MB, whereas Robo1 is expressed in the developing MB. The expression of Rig-1/Robo3, a negative regulator of Slit signalling, is upregulated in the prospective MB of Sim1/Sim2 double mutants,raising the possibility that the growth of mutant MB axons towards the midline is caused by a decreased sensitivity to SLIT. Finally, we found that Sim1 and Sim2 act along compensatory, but not hierarchical,pathways, suggesting that they play similar roles in vivo.

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Sim2 Contributes to Neuroendocrine Hormone Gene Expression in the Anterior Hypothalamus

Cited by 63 publications

References 39 publications

The zebrafish bHLH PAS transcriptional regulator, single‐minded 1 (sim1), is required for isotocin cell development

The zebrafish bHLH PAS transcriptional regulator, single‐minded 1 (sim1), is required for isotocin cell development

Dynamic expression of Thyrotropin‐releasing hormone in the mouse definitive endoderm

Sim1andSim2are required for the correct targeting of mammillary body axons

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