Building Blocks of Life: How Two Morphogen Gradients Create a Vertebrate Embryo
"New research reveals the minimal conditions needed to guide pluripotent cells into forming complete embryos using BMP and Nodal gradients."
The development of a vertebrate embryo is a marvel of biological engineering, relying on complex molecular and cellular processes. These processes progressively instruct embryonic cells, assigning their identities and dictating their behaviors. Over the past two decades, scientists have identified numerous genes critical to this intricate dance of development [1, 2].
However, the fundamental question remained: What are the minimal conditions required to coax pluripotent embryonic cells—cells with the potential to become any tissue in the body—into organizing themselves into distinct tissues and organs? This challenge was taken on by researchers, who sought to define the precise experimental conditions needed to construct a complete embryo. Their approach? Instructing early fish (Danio rerio) embryo cells using a carefully orchestrated combination of morphogenic signals.
The groundwork for this feat was laid nearly a century ago. In a pioneering experiment, Hilde Mangold, a student in Hans Spemann's lab, transplanted the dorsal blastoporal lip from one species of newt (Triturus taeniatus) into the ventral side of another (Triturus cristatus). This resulted in the formation of a secondary embryonic axis at the graft site, composed of both donor and host cells [3]. This groundbreaking work led to the dorsal blastoporal lip being defined as the 'organizer,' now known as the 'Spemann organizer,' for its ability to orchestrate the surrounding cells.
The Spemann Organizer: A Historical Perspective
The molecular nature of the Spemann organizer has been elucidated in recent decades [4]. Key to its organizing power are secreted factors released by the dorsal blastoporal lip. These factors act as antagonists to ventral morphogens, establishing a crucial ventro-dorsal activity gradient (Figure 1A). In Mangold and Spemann’s initial experiment, the dorsal factors secreted by the graft inhibited the ventral morphogens present at the graft site. This inhibition effectively created a new gradient, mirroring the morphogenic activity seen in the lateral and dorsal regions of a normal embryo (Figure 1B).
- However, when this organizer is grafted into a neutral environment, such as the animal pole of a zebrafish blastula, its activity is reduced, leading only to the formation of axial mesendodermal tissues like the notochord [5].
- This suggested that the organizing activity extends beyond the confines of the dorsal organizer.
- By grafting different portions of the zebrafish blastula or gastrula margin to the animal pole of a host blastula, it was discovered that the ventral margin acts as a caudal organizer [5].
- In contrast, the lateral and dorso-lateral regions of the margin organize the trunk and posterior head, respectively [6].
- This revealed that the embryo's organizing activities are not confined to the Spemann organizer, but are instead distributed along the entire margin, forming a continuum from the dorsal to the ventral territory [6].
Mimicking Nature: Building Embryos from Gradients
This research demonstrates the possibility of instructing pluripotent blastula cells using opposing gradients of morphogens like Nodal and BMP. By creating these gradients, the cells can be directed to organize into a complete embryo containing all the necessary tissues and organs. These factors act early in the process, sitting atop the cascade of gene regulations and inductions that characterize development. Thus, they are sufficient to initiate embryonic development and to induce and regulate, directly or indirectly, all the signaling pathways required to complete the developmental program.