Biology Dept
Kenyon College
Chapter 14B: Neurulation and
Limb Development
Fall Section Spring Section 1 Spring Section 2


Somites and Hox genes (below)

Neurulation in vertebrates results in the formation of the neural tube, which gives rise to both the spinal cord and the brain. Neural crest cells are also created during neurulation.  Neural crest cells migrate away from the neural tube and give rise to a variety of cell types, including pigment cells and neurons.

Neurulation begins with the formation of a neural plate, a thickening of the ectoderm caused when cuboidal epithelial cells become columnar. Changes in cell shape and cell adhesion cause the edges of the plate fold and rise, meeting in the midline to form a tube. The cells at the tips of the neural folds come to lie between the neural tube and the overlying epidermis. These cells become the neural crest cells. Both epidermis and neural plate are capable of giving rise to neural crest cells.

What regulates the proper location and formation of the neural tube? The notochord is necessary in order to induce neural plate formation.

from Patricia Phelps

Below are scanning electron micrographs of a chick embryo during neurulation.

During neurulation, somites form in pairs flanking the neural tube. Somites are blocks of cells that form a segmental pattern in the vertebrate embryo. Somites produce cells that become vertebrae, ribs, muscles, and skin.

The region where neural tube closure begins varies between different classes of vertebrates. In amphibians such as Xenopus, the neural tube closes almost simultaneously along its entire length. In birds, the neural tube closes in the anterior to posterior direction, as Hensen's node regresses. Mammalian neurulation is similar to that of birds, however the bulky anterior neural plate seems to resist closure - the middle of the tube closes first, followed by both ends. Watch this animation of mammalian neurulation!

From LIFE: The Science of Biology, 5th Edition, Purves et al., Sinauer Associates, 1998.

This video of a living Xenopus (frog) embryo shows both gastrulation and neurulation. You should recognize the beginning of the film from our discussion of gastrulation. The open neural plate on the dorsal side has formed by the time the blastopore closes. The closure of the neural plate into a tube is accompanied by elongation of the embryo.

from the Amphibian Embryology Tutorial

Another movie of Xenopus development is available here!

Somites and Hox genes (for review of chick embryo before somites, see here)
Hox gene chart
Paraxial mesoderm forms somites flanking neural tube
SEM of somites
Somites forming
Somite transplantation

Animal development: Organogenesis

Organogeneis is the period of animal development during which the embryo is becoming a fully functional organism capable of independent survivial. Organogenesis is the process by which specific organs and structures are formed, and involves both cell movements and cell differentiation. Organogenesis requires interactions between different tissues. These are often reciprocal interactions between epithelial sheets and mesenchymal cells.

The study of organogenesis is important not only because of its relevance to understanding fundamental mechanisms of animal development, but also because it may lead to medical applications, such as the repair and replacement of tissues affected by genetic disorders, disease or injury.

Kidney development

There are three stages of mammalian kidney development: the formation of the pronephros, mesonephros, and metanephros (nephros = kidney; pro = before, meso = middle, meta = after). The metanephros is the permanent kidney found mammals (and in birds and reptiles), and forms at the region between the mesonephros and the cloaca (below).

Balinsky's 1970 figure of mesonephric and pronephric anatomy from Peter Vize

The development of the adult kidney (metanephros) provides a good example of reciprocal epithelial-mesenchyme interactions. Mature (metanephric) kidneys form from reciprocal inductions between the metanephric mesenchyme and the (epithelial) ureteric buds.
The metanephric mesenchyme forms the nephrons, which are the functional units of the kidneys, and the (epithelial) ureteric buds form the collecting ducts and ureter.

Metanephric kidney development is a multistep process.
1. Mesenchyme cells induces the ureteric bud to elongate and branch.
2. The ureteric bud induces mesenchyme to aggregate (transition from mesenchyme to epithelium).

images from the Kidney Development Database

3. Each aggregate forms a nephron: first a comma shape is observed, and then the S-shaped tubule, which connects to the branched ureteric bud

images from the Kidney Development Database

What is the experimental evidence for reciprocal induction?
The metanephric mesenchyme doesn't condense into epithelial cells if cultured in isolation, but does if it is cultured with ureteric bud tissue. The ureteric bud doesn't branch if cultured in isolation, but does in combination with mesenchymal cells.
Similar experiments using a filter to separate the tissues showed that these inductions only work if cell processes can extend through the filter and directly contact the responding cells.

Vertebrate limb development

Vertebrate limbs develop from limb buds. The vertebrate limb bud consists of a core of loose mesenchymal mesoderm covered by an epithelial ectodermal layer. Cells within the progress zone rapidly divide, and differentiation only occurs once cells have left the progress zone. Because of this process, differentiation proceeds distally as the limb extends (that is, the proximal end of the limb develops before the distal end). The apical ectodermal ridge at tip of limb bud induces the formation of the progress zone.

Pattern formation organizes cell types into their proper locations based on positional information.

Anterior-posterior patterning is regulated by the zone of polarizing activity, or ZPA. The current model is that proximal-distal pattern formation is regulated by the amount of time a cell spends in the progress zone. Dorsal-ventral patterning is controlled by the overlying ectoderm.

What makes forelimbs and hindlimbs different from one another? Pattern formation is regulated by the same signals in both limbs, although these signals are interpreted differently. Limb-specific transcription factors have been identified, and by expressing these transcription factors in the OTHER (wrong) limb, scientists have been able to observe transformation of the hindlimb into the forelimb, and vice-versa.

left: Misexpression of Tbx4 in the forelimb region leads to leg-like structures in this region.
right: Misexpression of Tbx5 in the hindlimb region leads to wing-like structures in this region.

from the Max Planck Society

Thanks to David Marcey for construction of some of the images shown above