A face is unique to each person and is the basis of their own identity. However, the embryological origin is the same for all humans and is similar to other mammals. The development is complex and involves the formation and coordination of various tissues to form the final product. The functions of a face (and head) include hearing, vision, breathing, tasting, feeding, facial expression, and many more. Facial development happens very early during embryogenesis, and facial abnormalities can often be disfiguring and devastating. Treatment is often delayed until after the birth when the patient is stable. Some facial disorders are preventable and caused by teratogens; patients are therefore strongly discouraged from ingesting harmful substances or participating in risky behavior if they are pregnant or believe they may be pregnant. This activity will provide a brief overview of the embryology of facial development and some related pathologies.

The oropharyngeal membrane (where the face will eventually form) can already be seen on the embryo as early as week three, between the enlarging areas of the heart and the brain.[1] Facial embryology begins between weeks four and eight and involves a series of highly coordinated events based on preprogrammed data in cellular DNA. The process includes all the primary embryonic tissues, the ectoderm, endoderm, mesoderm.  

The oropharyngeal membrane is surrounded by several prominences (processes) that will eventually give rise to the face.

1. The frontonasal process rises from the neural crest and covers the forebrain. It will give rise to two medial nasal processes and two lateral nasal processes. The lateral nasal processes develop lateral to the nasal placode. The medial nasal processes develop medial to the nasal placode and will eventually fuse at the midline to form the inter-maxillary process. By the tenth week, the inter-maxillary process will form the nasal bridge and the philtrum of the upper lip.
2. The tissues of the 1st (mandibular) pharyngeal arch originates from mesoderm and the neural crest. The 1st arch will give rise two mandibular processes and two maxillary processes (proximal part of the arch). The maxillary processes will later form to a pair of palatal processes.

The nasal placodes are two ectodermal thickenings that appear at the end of the fourth week on the frontonasal processes.[2] These are precursors to the olfactory epithelium. The fifth week, the nasal placodes will be surrounded by the lateral and medial nasal swellings on the frontonasal process. Simultaneously, the maxillary processes from the mandibular branch of the 1st pharyngeal arch will develop and surround the oral cavity. The lower jaw will be formed early as a result of the two mandibular processes. The maxillary processes will also grow and meet the lateral nasal processes and extend midline to meet the medial nasal processes. This fusion with the medial nasal process will form the inter-maxillary process and result in the eventual formation of the philtrum of the upper lip.[1] If this fusion does not occur properly, an orofacial cleft may develop in the newborn. In the fifth week, the oropharyngeal membrane disintegrates, leaving behind a communication between the digestive tract and the external environment.

Additionally, the eyes initially are located on the side of the head but eventually face forward as the rest of the head grows and develops. By the end of developmental week seven, the embryo will have facial features that have a human appearance.

Palate:

The palate is the tissue between the nasal and oral cavity and is separated in the primary and secondary palates. By the 6th week, the inter-maxillary segment is formed from the fusion of the paired medial nasal prominences and the maxillary prominences. This epithelium will make the core of the primary palate, and posteriorly the nasal epithelium will touch the oral epithelium making the oro-nasal membrane.[2] Importantly, in the posterior region, the membrane will form an opening called the primitive choana that connects the oral cavity to the nasal cavity. The primary palate will also give rise to the anterior triangular one-third from the incisive foramen and include the four upper incisors. 

The secondary palate forms the rest of the hard palate and all of the soft palate and develops during the seventh and eighth weeks. It forms from two palatal shelves (medial outgrowths of the maxillary processes) that grow downward and parallel to the tongue. By the eighth week's end, the two secondary palatal processes fuse and with the primary palate to form the definitive palate. During this same time, the nasal septum grows to separate the left and right nasal passages, and its inferior portion will combine with the definitive palate.

It follows that if proper formation and fusion of the palates are necessary for healthy development and disruption may cause a cleft palate. Significant mechanisms that can cause a cleft palate include growth retardation and mechanical obstruction.

Pharyngeal apparatus:

Formed during the fourth week of development, consists of a mesenchymal tissue covered externally by ectoderm and internally by endodermal epithelium.

The pharyngeal clefts are produced from the approximation of ectodermal tissue between consecutive arches, while the pharyngeal pouches form from the approximation of endodermal tissue between consecutive arches. Derivatives of the apparatus relevant during facial development are described below: 

• Pharyngeal cleft: originate from the ectoderm. The first pharyngeal cleft gives rise to the external auditory meatus of the ear canal. The rest of the pharyngeal clefts form the cervical sinus. 

• Pharyngeal pouch: originate from the endoderm. The first pouch becomes the endoderm that lines the auditory and eustachian tubes, middle ear, and the inner layer of the tympanic membrane. The second pouch contributes to the middle ear.

• Pharyngeal arch: Originate from the mesoderm. The following arches develop into the varying adult structures.

1st: maxillary (V2) and mandibular (V3) branches of the trigeminal nerve (CNV), mandible, incus, malleus, muscles of mastication, maxillary artery, sphenomandibular ligament, the Meckel cartilage.

2nd: Facial nerve (CNVII), stapes, the body of the hyoid, lesser horn of hyoid, muscles of facial expression.

3rd: Hypoglossal nerve (CNIX), the body of the hyoid, greater horn of hyoid, stylopharyngeus muscle.

4th: superior laryngeal branch of the vagus nerve (CNX), thyroid, cricoid, arytenoid, cuneiform cartilage, levator veli platini, cricothyroid muscle.

6th: recurrent branch of the vagus nerve (CNX), thyroid, cricoid, arytenoid, cuneiform cartilage, larynx intrinsic muscles.[3]

Cranial neural crest cells or multipotent cells are fundamental for the development of facial tissues: bones, teeth, cartilage, connective tissue, and more. The cranial neural crest cells derive from the ectoderm leaflet from the dorsal midline portion. The cranial neural crest cells migrate towards pharyngeal arches and the frontonasal process; in this way, the tissues of the skull and the upper cervical tract form. In this event play critical role signaling pathways such as BMPs (bone morphogenic proteins); FGF (fibroblast growth factor); SHH (sonic hedgehog); WNT (wingless-related integration site). The ectodermal leaflet at week four covers the stomodeum, which ectoderm comes into contact with the endoderm leaflet, due to the development of the oropharyngeal membrane. During the fifth week, the ectoderm meets the mesoderm to start forming the nasal processes. Between the fourth and fifth week, the cells of the three main sheets meet to develop the different structures of the face.

The mechanism of chemical waves plays a vital role in the development process, that is, of mechanical-chemical information that transports information from one cell to another quickly. These waves or signals are patterns that help tissue morphogenesis. Probably, the management and initiation of these waves occur via chemical reactions at the centrosome level (MTOC - microtubule organizing center).

The ectodermal placodes, from which future sense organs and cranial ganglia will form, develop different molecular responses; in anterior areas, coding molecules will express as Pax (paired box protein), Six3 (homeobox protein SIX3), and Otx2 (homeobox protein OTX2). In the posterior portion of the placodes, we will find other molecules such as Irx1 / 2/3 (Iroquois-class homeodomain protein IRX-1) and Gbx2 (homeobox protein GBX-2). These proteins will help develop specific genes for specific functions.

For example, Pax6 will be more concentrated in the developmental areas of the sense of smell and the lens, while Pax3 and Pax2/8 will help to develop the trigeminal ganglia and the hearing area.