Snakes develop about 10x the number of somites as a chicken or mouse. Use the clock- wavefront model to explain the molecular basis of this evolutionary difference. First describe the model, citing experimental support as needed, and then explain how it is modified to produce additional somites in snakes. Solution The clock and wavefront model is a model used to describe the process of somitogenesis in vertebrates. Somitogenesis is the process by which somites, blocks of mesoderm that give rise to a variety of connective tissues, are formed. The model describes the splitting off of somites from the paraxial mesoderm as the result of oscillating expression of particular proteins and their gradients. Once the cells of the pre-somitic mesoderm are in place following by cell migration during gastrulation, oscillatory expression of many genes begins in these cells as if regulated by a developmental \"clock.\" This has led many to conclude that somitogenesis is coordinated by a \"clock and wave\" mechanism. More technically, this means that somitogenesis occurs due to the largely cell-autonomous oscillations of a network of genes and gene products which causes cells to oscillate between a permissive and a non-permissive state in a consistently timed-fashion, like a clock. These genes include members of the FGF family, Wnt and Notch pathway, as well as targets of these pathways. The wavefront progresses slowly in an anterior-to-posterior direction. As the wavefront of signaling comes in contact with cells in the permissive state, they undergo an epithelial-mesenchymal transition and pinch off from the more posterior pre-somitic mesoderm, forming a somite boundary and resetting the process for the next somite. In particular, the cyclic activation of the Notch pathway appears to be of great importance in the wavefront-clock model. It has been suggested that the activation of Notch cyclically activates a cascade of genes necessary for the somites to separate from the main paraxial body. This is controlled by different means in different species, such as through a simple negative feedback loop in zebrafish or in a complicated process in which FGF and Wnt clocks affect the Notch clock, as in chicks and mice.Generally speaking, however, the segmentation clock model is highly evolutionarily conserved. Intrinsic expression of “clock genes” must oscillate with a periodicity equal to the time necessary for one somite to form, for example 30 minutes in zebrafish, 90 minutes in chicks, and 100 minutes in snakes. somites form from the paraxial (somitic) mesoderm, a particular region of mesoderm in the neurulating embryo. This tissue undergoes convergent extension as the primitive streak regresses, or as the embryo gastrulates. The notochord extends from the base of the head to the tail; with it extend thick bands of paraxial mesoderm.As the primitive streak continues to regress, somites form from the paraxial mesoderm by \"budding off\" rostrally as somitomeres,.

1. Snakes develop about 10x the number of somites as a chicken or mouse. Use the clock-
wavefront model to explain the molecular basis of this evolutionary difference. First describe the
model, citing experimental support as needed, and then explain how it is modified to produce
additional somites in snakes.
Solution
The clock and wavefront model is a model used to describe the process of somitogenesis in
vertebrates. Somitogenesis is the process by which somites, blocks of mesoderm that give rise to
a variety of connective tissues, are formed.
The model describes the splitting off of somites from the paraxial mesoderm as the result of
oscillating expression of particular proteins and their gradients.
Once the cells of the pre-somitic mesoderm are in place following by cell migration during
gastrulation, oscillatory expression of many genes begins in these cells as if regulated by a
developmental "clock." This has led many to conclude that somitogenesis is coordinated by a
"clock and wave" mechanism.
More technically, this means that somitogenesis occurs due to the largely cell-autonomous
oscillations of a network of genes and gene products which causes cells to oscillate between a
permissive and a non-permissive state in a consistently timed-fashion, like a clock. These genes
include members of the FGF family, Wnt and Notch pathway, as well as targets of these
pathways. The wavefront progresses slowly in an anterior-to-posterior direction. As the
wavefront of signaling comes in contact with cells in the permissive state, they undergo an
epithelial-mesenchymal transition and pinch off from the more posterior pre-somitic mesoderm,
forming a somite boundary and resetting the process for the next somite.
In particular, the cyclic activation of the Notch pathway appears to be of great importance in the
wavefront-clock model. It has been suggested that the activation of Notch cyclically activates a
cascade of genes necessary for the somites to separate from the main paraxial body. This is
controlled by different means in different species, such as through a simple negative feedback
loop in zebrafish or in a complicated process in which FGF and Wnt clocks affect the Notch
clock, as in chicks and mice.Generally speaking, however, the segmentation clock model is
highly evolutionarily conserved.
Intrinsic expression of “clock genes” must oscillate with a periodicity equal to the time necessary
for one somite to form, for example 30 minutes in zebrafish, 90 minutes in chicks, and 100
minutes in snakes.
somites form from the paraxial (somitic) mesoderm, a particular region of mesoderm in the

2. neurulating embryo. This tissue undergoes convergent extension as the primitive streak
regresses, or as the embryo gastrulates. The notochord extends from the base of the head to the
tail; with it extend thick bands of paraxial mesoderm.As the primitive streak continues to regress,
somites form from the paraxial mesoderm by "budding off" rostrally as somitomeres, or whorls
of paraxial mesoderm cells, compact and separate into discrete bodies. The periodic nature of
these splitting events has led many to say to that somitogenesis occurs via a clock-wavefront
model, in which waves of developmental signals cause the periodic formation of new
somites.These immature somites then are compacted into an outer layer (the epithelium) and an
inner mass (the mesenchyme).The somites themselves are specified according to their location,
as the segmental paraxial mesoderm from which they form it itself determined by position along
the anterior-posterior axis before somitogenesis.The cells within each somite are specified based
on their location within the somite. In addition, they retain the ability to become any kind of
somite-derived structure until relatively late in the process of somitogenesis.
For some species, the number of somites may be used to determine the stage of embryonic
development more reliably than the number of hours post-fertilization because rate of
development can be affected by temperature or other environmental factors. The somites appear
on both sides of the neural tube simultaneously. Experimental manipulation of the developing
somites will not alter the rostral/caudal orientation of the somites, as the cell fates have been
determined prior to somitogenesis. Somite formation can be induced by Noggin-secreting cells.
The number of somites is species dependent and independent of embryo size (for example, if
modified via surgery or genetic engineering). Chicken embryos have 50 somites; mice have 65,
while snakes have 500.
As cells within the paraxial mesoderm begin to come together, they are termed somitomeres,
indicating a lack of complete separation between segments. The outer cells undergo a
mesenchymal–epithelial transition to form an epithelium around each somite. The inner cells
remain as mesenchyme.
Notch signaling-The Notch system, as part of the clock and wavefront model, forms the
boundaries of the somites. DLL1 and DLL3 are Notch ligands, mutations of which cause various
defects. Notch regulates HES1, which sets up the caudal half of the somite. Notch activation
turns on LFNG which in turn inhibits the Notch receptor. Notch activation also turns on the
HES1 gene which inactivates LFNG, re-enabling the Notch receptor, and thus accounting for the
oscillating clock model. MESP2 induces the EPHA4 gene, which causes repulsive interaction
that separates somites by causing segmentation. EPHA4 is restricted to the boundaries of
somites. EPHB2 is also important for boundaries.