Early this month, an article by Dr. Sekido and Dr. Lovell-Badge appeared in Nature, which is a break-through in the field of sex determination. Long-awaited question has been partially answered. How SRY sends signals downstream to direct male development has been explained. SRY is present for a brief period, but by the time it fades away there is sufficient SOX9 protein present to join forces with SF1 and bind to its own enhancer. In this way, SOX9 helps to maintain itself at a high level. SOX9 can then promote the activity of other genes responsible for cells developing into testes".
MRC news: http://www.mrc.ac.uk/NewsViewsAndEvents/News/MRC004565
http://www.ncbi.nlm.nih.gov/pubmed/18454134

Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer 
Sekido R, Lovell-Badge R. 
Nature. 2008 May 4. [Epub ahead of print] 

The mammalian Y chromosome acts as a dominant male determinant as a result of the action of a single gene, Sry, whose role in sex determination is to initiate testis rather than ovary development from early bipotential gonads. It does so by triggering the differentiation of Sertoli cells from supporting cell precursors, which would otherwise give follicle cells. The related autosomal gene Sox9 is also known from loss-of-function mutations in mice and humans to be essential for Sertoli cell differentiation; moreover, its abnormal expression in an XX gonad can lead to male development in the absence of Sry. These genetic data, together with the finding that Sox9 is upregulated in Sertoli cell precursors just after SRY expression begins, has led to the proposal that Sox9 could be directly regulated by SRY. However, the mechanism by which SRY action might affect Sox9 expression was not understood. Here we show that SRY binds to multiple elements within a Sox9 gonad-specific enhancer in mice, and that it does so along with steroidogenic factor 1 (SF1, encoded by the gene Nr5a1 (Sf1)), an orphan nuclear receptor. Mutation, co-transfection and sex-reversal studies all point to a feedforward, self-reinforcing pathway in which SF1 and SRY cooperatively upregulate Sox9 and then, together with SF1, SOX9 also binds to the enhancer to help maintain its own expression after that of SRY has ceased. Our results open up the field, permitting further characterization of the molecular mechanisms regulating sex determination and how they have evolved, as well as how they fail in cases of sex reversal.

Following whole genome sequence being publicly available, research in Medaka, a transparent small laboratory fish, has progressed tremendously. Medaka can be used for many aspect of biological and biomedial research, because of its transparent body, short generation turn over, daily production of eggs, transgenesis and robust XX/XY genetic sex determination system. Number of germ cells is the key issue for the process of sex differentiation- higher the germ cell number, higher the possibility of individuals being differentiated into females. Colleagues in National Institute for Basic Biology have shown that a protein, called Sdf1a plays key role in germ cell migration in Medaka. Several papers have been published by the same group regarding PGC migration in medaka in the year 2006 and 2007. Advances have been made slowly, and new factors have been identified which could be complementary to mammalian/avian germ cell research. Following article by Manfred Schartl`s group also seems interesting, which is a kind of follow-up of the previous finding by Tanaka group. Good work, Dr. Herpin!

Sequential SDF1a and b-induced mobility guides Medaka PGC migration.
Herpin A, Fischer P, Liedtke D, Kluever N, Neuner C, Raz E, Schartl M
. Dev Biol. 2008 Mar 28 [Epub ahead of print]

Assembly and formation of the gonad primordium are the first steps toward gonad differentiation and subsequent sex differentiation. Primordial germ cells (PGCs) give rise to the gametes that are responsible for the development of a new organism in the next generation. In many organisms, following their specification the germ cells migrate toward the location of the prospective gonadal primordium. To accomplish this, the PGCs obtain directional cues from cells positioned along their migration path. One such cue, the chemokine SDF1 (stromal cell-derived factor 1) and its receptor CXCR4 have recently been found to be critical for proper PGC migration in zebrafish, chick and mouse. We have studied the mechanisms responsible for PGC migration in Medaka. In contrast to the situation observed in zebrafish, where proper PGC positioning is the result of active migration in the direction of the source of SDF1a, Medaka PGC movements are shown to be the consequence of a combination of active SDF1a and SDF1b-guided migration. In this process both SDF1 co-orthologues show only partly overlapping expression pattern and cooperate in the correct positioning of the PGCs.

I read a news in Science Daily about the ban of Bisphenol A (BPA) in Canada and issues related to BPA and human health risks in the USA. My question is- are all those chemicals present in the environment at such a dose that humans are constantly exposed to? Most of the experiments have been perfomed using rodent models, and exposure are done either through IP injection or by incorporating those ultra-pure chemicals through diet  at way-too-high doses than that are available in the environment. Questions arise as to whether we should stick to those results. Why are not experiments being done at the dose that humans are exposed everyday to? These experimental designs will show the real effects of exposure on human health. 
My concern is- why scientists use the thousand times higher dose of chemicals in their experiment?- Just to know what the mechanism of action is? Any chemical if you are exposed to a significantly higher dose, no doubt, will alter the normal physiology and mechanism of your body. For a simple example, if a pregnant woman is given a pound of salt everyday for a month, the homeostasis of mother`s body fluid will change and consequently the baby will have some complication. Such effects may result in defective growth and abnormal functioning of body parts.  So, research designs that mimic real exposure to environmental concentration of toxic substances in human or non-human models will be highly appreciated. And, results that confirm previous finding in rats that exposure causes genetic imprinting and the disease state passes to subsequent generation will, however, be exciting. 

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