Lecture 5 - Mar 1.docx

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Cell and Systems Biology
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Dorothea Godt

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Lecture 5 – Mar 1 Sex determination in placental mammals Male or female = depends on whether we develop ovary or testis – the first sex-specific difference that develops - This is why it is called hte primary sex determination In early embryo, we have a bipotential gonad – can develop into testis or ovary and needs right trigger to go one or the other way After we have testis or ovary; these gonads promote the other sex-specific differences that occur later in development So we will look at some of these differences and what we know about how they are triggered Brennand and Capel Active lab in looking at early testis development (although we don’t know much about early ovary development) Few differences that become very obvious around time trigger is given either to testis development or ovary development (from mice gonads) In mammal tissue, sex is determined by the Y chromosome; so an XY genotype will develop a testis and XX an ovary A number of markers tell us the early differences that occur (BrdU) Cell Division Pattern (BrdU) BrdU = staining tells us where mitotic divisions occur during development, and BrdU is in red And can see in early testis, you can see more BrdU activity than XX ovary Cell Migration Gonad = flat structure that sits on top of the mesonephros (a part of the kidney only active during development and l;ater is replaced by something that forms the adult kidney – not that important just know gonad is difrectly ontop of this embyryonic kidney) These 2 organs interact with each others, gonad sends out signal that triggers the mesonephros (some of the cells become active) and migrate into the gonad where they form the vascular system (blood vessels!) - This is something that only happens in the testis, and here we have marker for meson (green) and can see some of the cells invade the gonad - This doesn’t happen in the XY Later on, we can see blood vessel formation on the surface of the testis (and this is important because the testis produces testoerone in early stages, and you need a carrier for this – the blood system) - This doesn’t happen in the XX eitherTestis Cord formation - Cubes that later develop into the tubule of the testis and are basically the carriers of the germ cells - These tubes only form in the testis and not the ovary Leydig cell differentiation These cells are important because they are the cells that produce the testosterone Based on all these markers, the ovary looks very passive, but this is actually only because the markers we are using are for the ovaries (keep that in mind) All these early changes are important, fore xample testis cord formation is important because they are tubes that contain the germ cells and thye can not mature without the correct environment (only inside the tubes, not outside) - Most important cells inside these tubules are the sertoli cells and they have many functions during male development and sperm maturation This picture summarizes the main cell types that form the gonadal tissue, and does not include tissue from the mesonphros (so blood vessels no shown here) So for both, we have our SGPs (somatic gonadal precursors, cells of the bipotential gonad) and PGCs (primordial germ cells and somatic germ.... something) So these cells need to be told to take on male or female pathways If trigger says go to male development, than the SGPs form 2 different cell types: sertoli cells (multiple functions in morphology, sperm development) and leydig cells (testosterone production) If trigger says go to female: 2 cell types also: granulosa cells and thecal cells (and have similar functions in female development as male development and these cells produce estrogen) If you think about testosterone and estrogen, they are associated with male and female respectively, but that’s wrong: males just have more testosterone than estrogen, and females have more estrogen than testosterone - Males do have estrogen, and they NEED it to produce and a number of sex-specific differences in brain - Females also NEED testosterone So both require both hormones, but testosterone or estrogen are respectively more important in male and females For PGCs These behave quite differently depending on whether they are in testis or ovary If in testis – they experience a block of meiosis and they can not enter meiosis, this is very important because if they enter meiosis they will overrun the and develop into ovaries (6:27) - So these PGCs undergo a few rounds of mitotic divisions (to produce a large pool of PGCs – spermatogonia or oogonia) but these spermatogonia they will eventually arrest BEFORE meiosis and remain in G0/G1 of mitotic cycle until pubertyIn females, on the other hand, PGCs do have mitotic divisions too (increase pool of PGCs) enter very early meiosis and arrest in prophase of meiosis 1 and remain in that phase until puberty, and during puberty individual oocytes become active and continue with their meiotic cycle - In females, there are also mitotic divisions to produce a large pool of PGCs (oogonia, and many die but we do not know why and only a small pool survive) and enters the prophase of meiosis 1 and remains at the stage until puberty So spermatogonia continue mitotic cycles and produce huge amounts of sperm and become stem cells (although not sure if they all become stem cells or not, but a certain number of spermatogonia become stem cells and then they become sperm cells) - Basically they arrest unti puberty and start again to divide, but now they enter a stem cell cycle (different form normal mitotic cells) - Important for them to become stem cells to produce a large amount of sperm (although its not clearly known how the niche works and what not) ASIDE: my opinon, this stem cell thing is probably not going to be tested because its not clearly known Difference between stem cell division and mitotic division: Mitotic division – 2 daughter cells are exactly the same Stem cell division – one cell will replenish old stem cell (so itself becomes a stem cell) and other daughter goes and produces whatever - Stem cell divisions always asymmetric division So sperm initially divide as mitotic (increase pool of PGCs) and then stem cell division to create sperm Developing ovaries and Developing testis (20 or 16 weeks) In female – already have ovarian follicles In testis – we have these tubule structures and the testis cord whidh develops into senifiiference tube) - These tubes are linked to which links it to the wolffian duct (involved in sperm transport through body) In female duct – this wolffian duct degenerates, and we develop the mullerian duct instead (which becomes the ovarian duct and other internal genital structures) In male – the mullerian duct degenerates So internal genitilia actually form from different structures (wolffian for male and mullerian for female) So very early on we see dramatic differences in these organs, and this is LONG before they presume their activity Primary and Secondary determination Primary sex determination – this is a genetic determination, if you have Y chromosome – triggers testis development and if we do not have a Y chromosome – we enter female developmentSecondary sex determination - The rest of these determined by whether we have a tetis or ovaries and these produce hormones which determine the internal and external genital structures and sexcondary sexual characteristics that develop during puberty
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