The problem of forming a stripe-like organizer for the dorsoventral axis: the vertebrate solution
Higher organisms have, as the rule, the geometry of a long stretched cylinder. An organizing region appropriate to generate the pattern for the mediolateral or dorsoventral axis must have the geometry of a long extended but narrow stripe. For many systems it has been shown that the midline can regenerate after removal [5-7], showing that the midline organizer has self-regulatory properties. What type of molecular interactions would be able to generate a region of high concentration that has a stripe-like geometry?
As shown, stripe formation can be accomplished by a pattern-forming reaction in which the self-enhancement saturates. On its own, however, such a stripe-forming system is still insufficient to generate a solitary straight stripe. Upon initiation by random fluctuations, somewhat meandering stripes would be formed that may bifurcate. The width of the stripes and the inter-stripe regions are of the same order, reminiscent of the ocular dominance columns, patterns on zebras or on some tropical fishes. The problem of multiple stripes cannot be circumvented by a strengthening of the lateral inhibition since this would lead to a decay of the stripe into individual patches.
Therefore, accessory pattern-forming reactions are required that allow the formation of just one stripe, the future midline organizer. It has been shown (Meinhardt, 2004, [ PDF] ) that the midline problem has been solved differently in different phyla. In vertebrates and insects (Drosophila) two pattern forming system are involved, one with a spot-like and one with a stripe-like characteristics. The spot-like organizer makes sure that only a single midline is formed.
In vertebrates a dorsal organizer initiates and elongates the midline towards anterior (prechordal plate) and towards posterior (the moving node). The mechanism for posterior midline formation may be compared with a high-flying airplane – a spot-like device – that leaves behind a stripe-like pattern – the vapour trail. The simulation above illustrates a simplified model. A spot-shaped activator (organizer, green) initiates a stripe-forming system (midline organizer, red) while the stripe forming system quenches the spot-forming system, enforcing its move in front of the tip of this incipient midline, and so on. In the course of time this process leads to the emergence of a single straight line.
The actual mechanism is more complex. Since the blastopore is at the early gastrula stage the most posterior structure, the spot-like Spemann-type organizer (dark green), localized on the blastopore, gives rise to an anterior and to a posterior part of the midline The first ingressing mesodermal cells move towards anterior. Those that were close to the organizer form the prechordal plate (yellow, Goosecoid expression) and thus the anterior part of the midline [1-3]. The posterior part of the midline (red) is left behind the moving organizer which contains a pool of stem cells that form in the course of time the notochord and the floorplate. The blastopore and the organizer (dark green) riding on them remain the most posterior structure (anterior is to the left, dorsal is up/front). Cells that forms the more lateral mesoderm move towards the organizer and the incipient midline by the convergence-extension movement (red arrows). In this way, the blastopore perpendicular to the AP axis becomes converted into the stripe-like posterior midline along the AP axis; the short thick cylinder becomes narrower and more extended .
Further Reading and References
Meinhardt, H. (2004). Different strategies for midline formation in bilaterians. Nat Rev Neurosci 5,502-510 [PDF]
- Kiecker, C. & Niehrs, C. (2000). The role of prechordal mesendoderm in neural patterning. Curr. Op. Neurobiol. 11, 27-33.
- Schulte-Merker, S., Hammerschmidt, M., Beuchle, D., Cho, K.W., De Robertis, E.M. & Nüsslein-Volhard, C. (1994). Expression of zebrafish goosecoid and no tail gene-products in wild-type and mutant no tail embryos. Development 120, 843-852.
- Artinger, M., Blitz, I., Inoue, K., Tran, U. & Cho, K.W.Y. (1997). Interaction of Goosecoid and Brachyury in Xenopus mesoderm patterning. Mech. Dev. 65, 187-196.
- Keller, R., Shih, J. & Sater, A. (1992). The cellular basis of the convergence and extension of the Xenopus neural plate. Dev. Dyn. 193, 199-217.
- Joubin, K. and Stern, C.D. (1999). Molecular interactions continuously define the organizer during the cell movements of gastrulation. Cell 98, 559-571.
- Psychoyos, D. and Stern, C.D. (1996). Restoration of the organizer after radical ablation of Hensen's node and the anterior primitive streak an the chick embryo. Development 122, 3263-3273.
- Yuan, S., Darnell, D.K. and Schoenwolf, G.C. (1995). Mesodermal patterning during avian gastrulation and neurulation: Experimental induction of notochord from non-notochordal precursor cells. Dev. Genetics 17, 38-54.