Craniofacial region
This region of developmental biology has more significance than some of the other areas that we have studied. The facial region is highly visible. Birth defects arise quite frequently in this area because of the complexity of its development. The visibility of the craniofacial region can lead to stress and difficulty for individuals and families with birth defects in this area.
BRANCHIAL APPARATUS- the key to understanding craniofacial development
During the fourth week of development, the human embryo has a series of bar-like structures present in the future pharyngeal region. These structures are located on the external surface of the embryo and they arch around the lateral sides of the pharynx. This is the area that represents the branchial apparatus.
These bars are called BRANCHIAL ARCHES. Each of these bars consists of an epithelial covering like a bag. These "bags" contain mesenchyme in their centers. It is somewhat like a bag of popcorn with the epithelial sheath pulling tight together like the bag and the popcorn inside represents the loosely packed mesenchyme.
The epithelial bag has an outer covering on the external side of the embryo composed of ectoderm. It also has an inner covering which is composed of pharyngeal lining (or the endoderm of the embryo). The mesenchyme that fills the bag is derived from two sources:
Branchial arches are numbered according to evolutionary studies. We therefore consider six branchial arches in series, numbered from rostral to caudal (Branchial arch #1 is most rostral and branchial arch #6 is most caudal).
The first arch (#1) becomes split on its ventral side into somewhat of a "Y" shaped structure. This region gives rise to two processes-- a rostral process called the MAXILLARY PROCESS (which develops in close association with the nose) and a more caudal process called the MANDIBULAR PROCESS.
-The Maxillary process gives rise the upper jaw or Maxilla
-The Mandibular process gives rise to the lower jaw or
Mandible
The split which separates these two processes is called the STOMODEUM. The stomodeum is an ectodermal invagination into the first branchial arches on each side.
The trick to understanding the branchial apparatus is to remember the three structures it comprises in alphabetical order.
-First come Branchial Arches
-Then come Branchial Pouches (or pharyngeal pouches)
And the Branchial Grooves (pharyngeal grooves)
In all cases, "A" for Arch comes before, and lies rostral to, the groove and the pouch. (note: the groove and pouch of a certain number lie together at the same level, the groove is an invagination of the epithelia from the outside of the embryo and the pouch is an evagination of the endoderm from the pharynx on the inside of the embryo). For example, most cranially in the branchial apparatus lies the first branchial arch. Just caudal to that lies the first branchial groove. Then just caudal to that lies the second branchial arch and then the second branchial groove.
After the third branchial arch in humans all of the rest of the branchial grooves are compressed into a single large groove called the CERVICAL SINUS.
The endodermal evagination which creates a branchial pouch will meet in the middle with an invagination of the ectoderm which creates a branchial groove. At this meeting point of the pouch and groove a thin membrane separates the two. This membrane is called the CLOSING PLATE. In other words the pouches and grooves are apposed to each other and the point of their contact is the Closing Plate. Or in other words again...grooves are ectoderm- lined spaces and pouches are endoderm-lined spaces and where the two meet is a closing plate.
The six pairs of aortic arches that we studied earlier run through the six branchial arches. The first, second, and fifth aortic arches are rudimentary. The third, fourth, and sixth aortic arches remain.
The above structures are some of the rudiments of the craniofacial region. Now we will discuss some of the modifications that these rudiments undergo.
The development of the face involves the formation of a series of five basic processes or prominences which arise from the branchial apparatus.
-One pair of mandibular processes (discussed above)
-One pair of maxillary processes (discussed above)
-A single midline FRONTAL NASAL PROCESS
The frontonasal process will subdivide into 5 more processes (at about the fourth or fifth week of gestation):
-A single FRONTAL PROMINANCE
-A pair of MEDIAL NASAL PROMINANCES
-A pair of LATERAL NASAL PROMINANCES
Between the maxillary processes and the mandibular processes there is an ectoderm-lined invagination called the STOMODEUM. A plate is formed where this ectodermal invagination meets the pharyngeal endoderm in the midline. This plate is composed of both endoderm and ectoderm and is called by many names: Buccopharyngeal membrane, ORAL MEMBRANE (preferred name), etc. This membrane ruptures to give rise to the mouth opening.
Just rostral to the oral membrane in the midline is the Frontal nasal prominance.
The way to develop the face is to bring all of these processes together in an ordered fashion with a series of fusions.
The lower jaw is derived from the mandibular swellings in a simple way making lower jaw anomolies rare. The two swellings merge together in the midline and fuse to make a single lower jaw. One of the only anomolies associated with the lower jaw is HYPERFUSION of the lower jaw. Many, probably most, people have this "defect" as evidenced by a lack of a dimple in the center of the lower jaw. (example of what we find as "normal" depends on cultural standards--quite arbitrary)
The upper jaw is much more complex because more processes need to come together (All of the frontal nasal processes and the maxillary processes). This takes place during the sixth to twelvth weeks. The frontal nasal process now gives rise to its five processes and to ridges which wrap around the NASAL PITS (rudiments of the nose). The upper jaw is formed by merging the two medial nasal processes together. In addition the maxillary swellings are going to sneak across the nasal pit to fuse with the merged medial nasal processes. This is usually where the defects of cleft lip occur. In people without this defect you can feel a ridge where the fusion occured between the maxillary processes and the medial nasal processes.
The cheeks form by enlargement of the maxillary processes.
The frontal process grows down to give rise to the forehead region.
A number of processes come together to give rise to the nose. The center of the nose is formed from the two medial nasal processes (which also gives rise to the upper jaw). We also have enlargement of the lateral nasal processes to give rise to the sides of the nose. As they do that, the cheek and lateral nasal bones need to fuse together or you may have an OBLIQUE FACIAL CLEFT which extends from the corner of the eye all the way down to the oral cavity (fairly rare).
This whole process occurs during the 4th to 12th week of gestation. By the 12th week the embryos look human based on their facial features yet they are small (they go from 1/6 of an inch to about 3 1/2 inches long). As the face is forming there is a tremendous amount of growth occuring in the embryo. The trick is for the embryo to grow in the right proportion in the right place in order for all of these processes to come together in a normal way.
Palate
Cleft palate is fairly common 1 in 2500 kids. Formation of the palate involves a major fusion that is fairly simple to understand. The fusion is like the space shuttle doors. Two large PALATAL SHELVES grow out in a vertical orientation on either side of the tongue. As the oral cavity grows, enough space is made in the cavity to cause these shelves to reorient themselves in a horizontal plane (major problem causing step). As this vertical to horizontal twisting occurs, the two shelves must be correctly aligned so that continued growth will bring them together in the midline for fusion to occur. Problems both outside and inside the palatal shelves themselves can cause reorientation of these structures.
Craniofacial syndromes
The key element seems to be sensitivity of neural crest cells. This is evidenced by babies with defects of the craniofacial region and the outflow tract of the heart because the partitioning of the outflow tract of the heart is done by neural crest.
A number of genetic factors influence these defects but also a number of environmental factors may be involved. It is important to remember that Vitamin A (Retinoic acid) is a potent teratogen. The oral (not topic) use of Accutane for acne in women of reproductive age is not recommended
Patterning of the Craniofacial region
The reason you get a normal or abnormal face is because of differential growth among the various rudiments. There are essentially two ways to get dismorphogenesis--genetic perturbation or environmental perturbation. That which is normal is based on society. For example two different dogs have the same embryology, but a greyhound has much more growth of the nose than does a mastif.
Differential growth is controlled by differences in cell behavior (cell death, migration, change in shape and size, etc.). If you perturb any of these things, the likely outcome is going to be some kind of birth defect.
The way to regulate cell behaviors is to utilize secreted molecules (morphogens: growth factors or sickling molecules) that form concentration gradients. These morphogens are diffusable within the embryo, and they bind to receptors on cells and initiate signaling pathways within the cell which result in regulation of gene expression (stimulate or suppress transcription factors). One class of transcription factors are the Homeotic or Hox genes which are expressed in a sequential manner. This pattern of expression is involved in the paterning of the craniofacial region. These genes are expressed in the hindbrain region in different levels. Then neural crest cells migrate out and carry the pattern with them to the branchial arches. So if you have a defect in Hox genes, you will have a defect in neural crest, and this effects branchial arches which effects the craniofacial region.