Thursday, August 16, 2007

The gender bending urbisexuals

No I'm not talking about metrosexual urbanites but of the hypothetical ancestor of animals with bilateral symmetry (as opposed to radial symmetry like sea urchin). The urbilateria is one of my favorite ideas in evo-devo. I like it because this mystical beast is purely a construct of inference, much like particle physic's Higgs Boson. The idea is that by looking at existing clades and phyla of protostomes and deuterostomes we can imagine what the common ancestor might have looked like. For example, maybe it had segments, and antennae, a mouth, two eyes. But what I really wonder is how did it have sex? Was the urbilateria a hermaphrodite? did it have external or internal fertilization? But the question I'm most interested in, is how his germ cells and stem cells operated. See there are two ways of making germ cells: preformation and epigenesis. In the former it is the asymetric distribution of germ plasm (coming from the oocyte) during cell division that makes the germ cell, while in the latter it is signals (BMPs) coming from the epiblast which directs dedifferentiation into germ cells. Extavour and Akam think that our ancestor used epigenesis, and that preformation reevolved several times, by simply maintaining maternal expression of germ cell genes like nanos and vasa in the zygote.

There must however be a tradeoff in keeping totipotent stem cell genes expressed in germ cells such as nanog, sox2, oct4. Quite likely that tradeoff is the risk of teratocarcinoma, which is the bizarre cancers deriving from germ cells. Great measures are taken to control germ cells and stop them from either differentiating into somatic cells or turning into cancers. Primordial Germ Cells (PGCs) are mostly transciptionally silent. They have vast changes in their chromatin structure, and very specific changes in histone and DNA methylation. In fact their embryonic precursors don't even express the stemness genes, those need to be reactivated by the BMP signal. To simplify, the stemness of the ES cell is a great liability and is quickly erased by down regulating master genes, only later does the germ cell regain this ability but at the cost of becoming transcriptionally silent. Futhermore, the migration of PGCs to the gonadal ridge acts as a second barrier to weed out potentially defective germ cells. Many germ cells get lost and die during that process. They must get there to be rescued by paracrine signals within a very narrow time. Futhermore even within the adult most female germ cells remain transcriptionally silent. Male germ cells which must remain active and divide have evolved a special DNA methylation system to keep retrotransposons in check, and they are particularly prone to apoptosis at pachytene if anything goes wrong, which means males are more susceptible to acute environmental exposure to sterilizing substances. Interrestingly germ cells also lack interferon sensitivity which has led to the evolution of a whole gamut of non-coding RNA regulation. There are about 50 000 piRNAs which regulate germ cells and we know almost nothing about. I've been looking at a possible link between large scale changes in chromatin that occur in germ cells and piRNA as a potential comprehensive exam topic. It really blows my mind.

So where does that leave our poor urbilateria. Well perhaps it had only one type of stem cell interspersed through its body and those stem cells were mostly silently waiting for an injury, but also capable of producing germ cells. We wont know for sure until synthetic biology as grown enough for us to recreate hypothetical ancestors...