Embryogenesis

Several new advancements in our understanding of development were reported this week, including a startling revelation about the neural development of gender, the discovery of a signalling molecule that transforms midbrain to hindbrain (the region that becomes the cerebellum), and a glimpse into the cause of a common neural tube birth defect.

The "neural tube" is a stage in the development of the embryonic brain; the brain begins as a relatively undifferentiated sheet of cells on the dorsal surface of the embryo. Known as the neural plate, this structure is visible when the embryo is less than 1 cm long. The plate then folds in on itself to become the neural groove, which fills with cerebrospinal fluid and eventually closes to become the neural tube. This process completes within only 25 days of conception.

This structure will begin to swell at three distinct points along its length (one for forebrain, one for midbrain, and one for cerebellum & pons) and eventually will bend backwards to create a shape more characteristic of the adult brain. As each swelling differentiates into various brain regions, the newest cells (called neuroblasts) begin in the center of the neural tube and must migrate outwards: miraculously, the brain constructs itself inside-out. How each baby neuron finds its way from the center of the neural tube, crawling past all the other neurons, and ultimately finds it resting place on the outermost layer of the new brain is still a topic of intense debate.

One of the most common defects in this complex process is that new cells may not begin at the midline of the neural tube. This causes 1 in every 20 spontaneous abortions, and maybe the neural tube defects seen in every 1 out of 1000 births. These "lost neuroblasts" may become misplaced because the polarity of the cell is lost during cell division; new cells therefore lack the information to determine which way is up. A paper from Nature demonstrates how polarity is restored to new cells, based on an asymmetrical migration of proteins shortly after cell division.

Another new paper this week shows how subtypes of a signalling molecule known as FGF8 have differential effects on the neural tube, such that FGF8a causes midbrain to grow, while FGF8b can transform midbrain cells to hindbrain cells. Given that other FGF8 isoforms exist throughout the embryo, this has implications for our understanding of the mechanisms modulating embryogenesis.

Yet another paper demonstrated how estrogen interacts with a protein known as alpha-fetoprotein (AFP) to "feminize" or "masculinize" the developing brain. When female mice that were incapable of producing AFP were injected with extra estrogen and surrounded by sexually active males, they showed no interest in sex and furthermore would even try mounting other females! Female mice that were both AFP-deficient and denied estrogen in the womb, however, showed normal female behavior. These findings indicate that the presence of estrogen masculinizes the brain, and the presence of AFP counteracts that effect. The role of other sex hormone binding proteins may be similar.