Embryology and development of the facial skeleton

Key points

• The embryological components of the facial skeleton are derived from the three divisions of the skull: the desmocranium, the chondrocranium and the viscerocranium.

• The ectomeninx has chondrogenic and osteogenic properties which translate into intramembranous bone that forms the skull vault or calvaria.

• The facial bones develop intramembranously from the ossification centers in the neural crest mesenchyme of the embryonic facial prominences.

• The mandible is derived from ossification of the osteogenic membrane formed from ectomesenchymal condensation around the Meckel cartilage.

The complexity of the facial skeleton that challenges the practice of aesthetic surgery is derived from its embryologic origins. The embryologic components of the facial skeleton are derived from the three divisions of the skull: the desmocranium, the chondrocranium, and the viscerocranium ( Fig. 15.1 ). , The roles of growth factors in craniofacial development are explored in bones, glands, and organs. The evolution of the head is revealed by the gradual acquisition of neural crest regulatory circuits.

Fig. 15.1

Main developmental divisions of the skull.

The classic embryonic tissues of ectoderm, mesoderm, and endoderm are variably integrated into facial development. An additional neural crest population contributes to the eventual formation of bone, cartilage, connective tissues, and muscles of the face. The cranial ectoderm provides the covering epidermis of the skull and the lining of the nasal and oral cavities.

The emergence of molecular genetics and gene identification has allowed for the designation of components of the embryologic origins of the different facial structures. The advances in gene-centric biologic insights integrated with analysis of genome-wide data have allowed for a systems level elucidation of facial development. , Genetic programs are instrumental in the stepwise endochondral and intramembranous ossification of the facial skeleton. ,

Branchial arches and pharyngeal pouches

The ventral foregut of the somite period embryo becomes segmented into six pharyngeal (branchial) arches that surround the central pharynx. The branchial arches form the middle and lower thirds of the face. Later development of the fetal face is explored from newborn to adulthood. An overview of the molecular interactions responsible for facial development is detailed by Som et al.

Both endochondral and intramembranous ossification programs are used to form different aspects of the facial skeleton. The cranial neural crest, having undergone an epithelial-to-mesenchymal transition, proliferates and migrates from the dorsal neural ectoderm into the facial prominences to become the precursors of the chondrocranium. Mesenchymal stem cells in a sequential program aggregate and undergo condensation obtaining a critical mass to differentiate into chondrocytes mediated by epithelio-mesenchymal signaling forming anlagen. , The complex genetic program is coordinated by signaling cues that include members of the bone morphogenetic protein (BMP) signaling family as well as Wingless/WNT signaling factor and fibroblast growth factor (FGF). These patterning cues positively influence key transcriptional regulators such as SOX9 and family members (SOX5 and SOX6), as well as RUNX2 and DLX family members. These factors regulate the laying of fibril-forming collagen (COL2A1 and family members), infusing the extracellular matrix, which results in chondrocyte differentiation. The chondrocyte proliferation and hypertrophic maturation phases of development are mediated by the parathyroid hormone (PTH) signaling pathway. Additional markers of ossification, including transcription factors OSX2, as well as MSX and DLX family members, which are involved in the continued differentiation and patterning of anlagen, are expressed. Enlarged hypertrophic cells further differentiate, mineralizing the surrounding extracellular matrix, and either transform into osteoblasts or become apoptotic. The surrounding perichondrial cells differentiate into osteoblasts encouraging angiogenesis via vascular endothelial growth factor (VEGF) and expressing matrix metalloproteases (MMPs) signifying the replacement of the initial chondrocyte anlagen with mineralized bone matrix. ,

Intramembranous flat bones of the skull are formed from mesenchymal cells that undergo condensation and directly differentiate into osteoblasts that deposit the mineralized matrix ( Fig. 15.2 ). Osteocytes produce collagen type I (COL1A1), osteocalcin, osteonectin, and bone sialoprotein, which make up the bone extracellular matrix, which is then remodeled by osteoclasts derived from hematopoietic stem cells.

Fig. 15.2

Schematic overview of endochondral and intramembranous ossification genetic programs, including key factors that and markers of differentiation. ACAN, Aggrecan; ALP, alkaline phosphatase; ATF4, activating transcription factor 4; BMPs, bone morphogenetic family members; COL1A1, collagen type 1; COL2A1, collagen type 2; COLX, collagen type 10; FGFs, fibroblast growth factors; GDF5, growth differentiation factor 5; IHH, Indian hedgehog; LRP5/6, low density lipoprotein receptor-related protein 5 and 6; MSX2, muscle segment homeobox 2; NCAD, neural cadherin (CDH2); NCAM, neural cellular adhesion molecule; OSX, osterix; PTH, parathyroid hormone; RUNX2, runt related transcription factor 2; SOX, SRY-Box related factors; TGF β , transforming growth factor beta; TWIST1, twist transcription factor 1; VEGF, vascular endothelial growth factor; VitD 3 , vitamin D; WNT and WNT10b, wingless signaling family members.

Facial derivation from the embryonic frontonasal, maxillary, and mandibular prominences is based on the contributions of the ectoderm and mesenchymal tissues. The facial ectoderm provides the detailed signaling to the underlying mesenchyme to create the morphogenetic movements of the facial prominences and alignment of structures preceding fusion to compose the face. Divergence from the complexity of signaling, morphogenesis, growth, and fusion accounts for the creation of craniofacial defects.

The skeletal and connective tissues of the face are dependent on dorsally located neural crest tissue migrating as ectomesenchyme in the ventral regions of the future skull, face, and neck. Any deficiencies in the quantity and quality of the migrating ectomesenchyme manifests itself in a wide range of congenital anomalies expressed as minor or major clefts of the face.

The calvaria

The calvaria of the frontal portion of the facial skeleton is derived from the outer (ectomeninx) and inner (endomeninx) coverings of the brain. The ectomeninx has chondrogenic and osteogenic properties, which translate into intramembranous bone that forms the skull vault or calvaria ( Figs. 15.3–15.6 ).

Fig. 15.3

Lateral view of neonatal skull.

Fig. 15.4

Calvaria frontal bones and metopic suture in an 8-week-old fetus.

Fig. 15.5

Lateral view of 12 week fetus (CRL 9.1 cm) stained for cartilage (Alcian blue) and bones (Alizarin red).

Courtesy Dr. V. M. Diewert.

Fig. 15.6

Dorsal view of neonatal skull depicting the sagittal and parietal suture sites.

The midface

The chondrocranium contributes to the midfacial components of the skull, the ala nasal cartilages, the nasal septum, and otic capsules. The otic capsules chondrify and fuse with the parachordal cartilages to ossify later as the mastoid and petrous portions of the temporal bones. The optic capsule does not chondrify or ossify in humans. The ossifying chondrocranium meets the ossifying desmocranium to form the neurocranium ( Fig. 15.7 ).

Fig. 15.7

Schema of adult cranial base indicating sites of primordial cartilages of chondrocranium (in black) and extent of endochondral (light stipple) and intramembranous (heavy stipple) ossification.


The division of the initial oronasopharynx into upper nasal and lower oral compartments is effected by the palatal shelves arising bilaterally from the embryonic midfacial region. The initially bilateral vertical palatal shelves elevate into the horizontal position meeting in the midline and fusing to form the definitive palate ( Fig. 15.8 ). Failure of fusion leads to varying degrees of cleft palate. ,

Apr 1, 2021 | Posted by in Aesthetic plastic surgery | Comments Off on Embryology and development of the facial skeleton
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