Pressure as a Developmental Agent
Gravity and pressure
In Chapters 7 and 8, we saw that gravity is critical for frog and chick axis formation. There are also several bones whose formation is dependent on pressure from the movement of the embryo. Such stresses are known to be responsible for the formation of the human patella (kneecap) after birth and have also been found to be critical for jaw growth.* Abnormal muscle and joint forces on bones have been seen as causing the numerous bone deformities that afflict children with cerebral palsy after birth (Shefelbine and Carter 2004). Vertebrate cartilage cell differentiation and cartilage matrix production depend on mechanosensitive interactions among a number of genes and gene products. One of the most important of these genes is Sox9, which is upregulated by compressive force (Takahashi et al. 1998). The Sox9 protein activates numerous bone-forming genes (see Chapter 11). Tension forces also activate bone morphogenetic proteins (BMPs) and align chondrocytes (Bard 1990; Sato et al. 1999; Ikegame et al. 2001). Several studies implicate indian hedgehog as a key signaling molecule that is stimulated by stress and which activates the bone morphogenetic proteins (Wu et al. 2001).
In the chick, several bones do not form if embryonic movement in the egg is suppressed. One of these bones is the fibular crest, which connects the tibia directly to the fibula. This direct connection is believed to be important in the evolution of birds, and the fibular crest is a universal feature of the bird hindlimb (Müller and Steicher 1989). When the chick is prevented from moving within its egg, the fibular crest fails to develop (Figure 1; K. C. Wu et al. 2001; Müller 2003).
Mechanical stress is also important for the differentiation of smooth muscle. Smooth muscle develops at sites of continuous mechanical tension, such as the vasculature and viscera. In the lungs, the pressure generated by breathing is necessary for bronchial smooth muscle development (Yang et al. 2000). These smooth muscles develop from bipotential mesenchymal cells that can become either adipocytes (fat cells) or myocytes (muscle cells). Physical pressure induces the cells to become muscles by differentially expressing two proteins, TIP1 and TIP3. TIP1 is induced by mechanical stress, binds to and activates the promoter regions of myogenic genes, and causes the mesenchyme cells to follow the myogenic pathway. TIP3, an activator of fat-producing genes, is repressed by mechanical stress. In the absence of such stress, the cells to become adipocytes (McBeath et al. 2004; Jakkaraju et al. 2005). Therefore, even in the formation of important features such as bones and muscles, the environment can play a critical role.
In Chapter 12, we discussed numerous examples of when pressure is required for the development of blood vessels and portions of the heart. In addition, Lucitti and colleagues (2007) have shown that hemodynamic force is needed for the remodeling and expansion of the blood vessels surrounding the yolk sac. By lowering the fluid pressure in the yolk blood vessels, they prevented blood vessel growth and remodeling.
Lucitti, J.L., E. A. Jones, C. Huang, J. Chen, S.E. Fraser, and M.E. Dickinson. 2007. Vascular remodeling of the mouse yolk sac requires hemodynamic force. Development 134: 3317–3326.
*Normal human jaw development may be predicated on expected tension due to grinding food. Mechanical tension appears to stimulate indian hedgehog expression in the mandibular cartilage and this paracrine factor stimulates cartilage growth (Tang et al. 2004). If infant monkeys are given soft food, their lower jaw becomes smaller than usual (Corrucini and Beacher 1982 1984). Those authors and Varella (1992) have shown that people in cultures where infants are fed hard food have jaws that “fit” better, and speculate that soft infant food explains why so many children in Western societies need braces on their teeth. The notion that mechanical tension can change jaw size and shape is the basis of the functional hypothesis of modern orthodontics (Moss 1962, 1997).