HMG-CoA reductase guides migrating primordial germ cells

@article{Doren1998HMGCoARG,
  title={HMG-CoA reductase guides migrating primordial germ cells},
  author={Mark. Van Doren and Heather T. Broihier and Lisa A. Moore and Ruth Lehmann},
  journal={Nature},
  year={1998},
  volume={396},
  pages={466-469}
}
The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is best known for catalysing a rate-limiting step in cholesterol biosynthesis, but it also participates in the production of a wide variety of other compounds. Some clinical benefits attributed to inhibitors of HMG-CoA reductase are now thought to be independent of any serum cholesterol-lowering effect,. Here we describe a new cholesterol-independent role for HMG-CoA reductase, in regulating a developmental process: primordial… 
Isoprenoids control germ cell migration downstream of HMGCoA reductase.
TLDR
The specificity and evolutionary conservation of the HMGCoAr pathway for germ cells suggest that an attractant common to invertebrates and vertebrates guides germ cells in early embryos.
Developmental processes regulated by the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) pathway: highlights from animal studies.
TLDR
A synthesis of recent animal and in vitro studies has yielded valuable insights into potential morphogenic parameters that are modulated by HMGCR activity, and it is hoped that this review will highlight the need to comprehensively examine the entire suite of developmental processes regulated by H MGCR.
Inhibition of HMG CoA reductase reveals an unexpected role for cholesterol during PGC migration in the mouse
TLDR
Cholesterol was measured in living tissue dissected from mouse embryos and was found to accumulate within the developing gonads as germ cells migrate to colonize these structures, demonstrating that during gestation, the cholesterol required for PGC migration can be supplied maternally.
Early Embryonic Lethality Caused by Targeted Disruption of the 3-Hydroxy-3-methylglutaryl-CoA Reductase Gene*
TLDR
It is speculated that the putative peroxisomal reductase gene, if existed, does not fully compensate for the lack of the ER enzyme at least in embryogenesis, and the haploid amount of Hmgcr gene is not rate-limiting in the hepatic cholesterol homeostasis.
HMGCoA reductase potentiates hedgehog signaling in Drosophila melanogaster.
TLDR
It is shown that Drosophila HMGCoA reductase functions in the hedgehog (hh) signaling pathway, and there are substantial germ cell migration defects in trans combinations between hmgcr and mutations in different components of the hh pathway.
Germ cell migration in zebrafish is dependent on HMGCoA reductase activity and prenylation.
TLDR
It is shown that pharmacological HMGCoAR inhibition alters zebrafish development and germ cell migration and highlights a conserved role for protein geranylgeranylation in this context.
Ovarian 3-hydroxy-3-methylglutaryl-CoA reductase in Blattella germanica (L.): pattern of expression and critical role in embryogenesis.
TLDR
The results suggest that fluvastatin is incorporated into the oocytes and has delayed inhibitory effects on the oviposited eggs, suggesting that HMG-CoA reductase is essential for embryogenesis, but not for chorion formation.
Functional analysis of Niemann-Pick disease type C family protein, NPC1a, in Drosophila melanogaster
TLDR
The Niemann-Pick disease type C-1a (NPC1a) protein is involved in embryonic germ cell migration and Hedgehog signaling in Drosophila melanogaster and it is shown that mesoderm-specific inactivation of Npc1a results in germcell migration defects.
Peroxiredoxin stabilization of DE-cadherin promotes primordial germ cell adhesion.
TLDR
In vivo evidence of a peroxiredoxin regulating DE-cadherin-mediated adhesion is presented and biochemical evidence strongly suggest that Jafrac1-mediated reduction of H₂O₁ is required to maintain DE- cadher in protein levels in the early embryo.
The hedgehog Pathway Gene shifted Functions together with the hmgcr-Dependent Isoprenoid Biosynthetic Pathway to Orchestrate Germ Cell Migration
TLDR
Investigation of the role of the hedgehog (hh) pathway gene shifted (shf) in directing PGC migration shows that production of this PGC attractant depends upon shf as well as a second hh pathway gene gγ1, and evidence indicating that ectopic expression of hmgcr in the nervous system promotes the release/transmission of the Hh ligand from these cells into and through the underlying mesodermal cell layer.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 18 REFERENCES
Developmental and metabolic regulation of the Drosophila melanogaster 3-hydroxy-3-methylglutaryl coenzyme A reductase.
TLDR
Two HMG CoA reductase mRNA transcripts were differentially expressed throughout Drosophila development, and Mevalonate-fed Schneider cells showed a parallel reduction of both enzyme activity and abundance of the 4-kilobase mRNA transcript.
Human mesangial cell production of monocyte chemoattractant protein-1: modulation by lovastatin.
TLDR
Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase by lovastatin resulted in a reduction of the mesangial cell-derived chemotactic activity as well as MCP-1 mRNA expression, suggesting a role for isoprenoid intermediates of the mevalonate pathway and/or isiprenylated proteins in mesangia cell MCP1 regulation.
Non-lipid-related effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.
TLDR
Results suggest that, beyond their effects on plasma lipids, HMG-CoA reductase inhibitors exert a direct antiatherosclerotic effect on the arterial wall, probably through local inhibition of isoprenoid biosynthesis.
The 412 retrotransposon and the development of gonadal mesoderm in Drosophila.
TLDR
The maintenance of high levels of 412 expression in gonadal mesoderm is not induced by contact with germ cells, but rather depends on genetic control by the homeotic genes abdominal-A and Abdominal-B.
zfh-1 is required for germ cell migration and gonadal mesoderm development in Drosophila.
TLDR
It is shown that zfh-1 acts in conjunction with tinman, another homeodomain protein, in the specification of lateral mesodermal derivatives, including the gonadal mesoderm, which facilitates the migration of germ cells from the endoderm to the Mesoderm.
Regulation of zygotic gene expression in Drosophila primordial germ cells
TLDR
This work addresses the issue of onset of zygotic transcription in somatic cells by localizing the potent transcriptional activator Gal4-VP16 to the germline, and finds that Gal 4-VP 16-dependent gene expression is repressed in early germ cells, even in the presence of known transcriptionalactivators.
Germ cell development in Drosophila.
TLDR
This review addresses various aspects of germ cell development in Drosophila, such as germ cell determination, germ cell migration, gonad formation, sex determination, and gametogenesis.
Identification of genes controlling germ cell migration and embryonic gonad formation in Drosophila.
Gonadogenesis in the Drosophila embryo is a complex process involving numerous cellular migratory steps and cell-cell interactions. The mechanisms guiding germ cells to move through, recognize and
Regulation of the mevalonate pathway
TLDR
The mevalonate pathway produces isoprenoids that are vital for diverse cellular functions, ranging from cholesterol synthesis to growth control, and could be useful in treating certain forms of cancer as well as heart disease.
The Drosophila protein Wunen repels migrating germ cells
TLDR
The protein Wunen has two properties that allow it to use repulsion to guide the germ cells, and is expressed in the gut in a pattern that guides germ cells towards the mesoderm.
...
1
2
...