Vertebrate Embryo: Craniofacial Development

Abstract

Craniofacial development requires the co‐ordinated integration of signals from the endoderm, mesoderm, ectoderm, neuroectoderm and neural crest cells (NCCs). Reflecting this complexity, craniofacial abnormalities are leading causes of birth defects and infant mortality. As the craniofacial complex shares tissue origins with the heart, craniofacial defects are often linked to cardiac defects. The key steps in craniofacial development and evolution include the generation, migration and differentiation of NCCs, and the dynamic interplay between signals in the NCC and the endoderm, ectoderm and mesoderm. The NCC determine species diversity whilst signals from the endoderm determine which facial structures are formed. Reflecting the evolutionary novelty of the head, the mechanisms of musculoskeletal development are also distinct from the trunk. Key Concepts The vertebrate head arose due to the evolution of neural crest and sensory placodes. Neural crest cells are a transient population of multipotent cells that give rise to most of the derivatives of the face and neck. The neck and lower jaw are formed from pharyngeal arches, transient structures that arise in a rostral‐caudal sequence. The pharyngeal arches initially consist of mesoderm, ectoderm, endoderm and neural crest. Each of these tissue layers gives rise to different derivatives. The cranial neural crest arises from the forebrain, midbrain and hindbrain. The neural crest streams migrate along stereotypical paths into the developing face and pharyngeal arches. Patterning of the pharyngeal arches 2, 3, 4 and 6 is determined by Hox genes. The developing face (pharyngeal arch 1 or mandibular primordia, maxillary primordia, lateral and medial processes) does not express Hox genes. The face is patterned by homeobox genes. Growth factors, for example SHH, FGF8, ENDOTHELIN‐1 and BMP4 control the growth of the face (cell survival and proliferation) through epithelial–mesenchymal signalling interactions and patterning via regulation of homeobox gene expression. Signals from the early endoderm pattern the facial primordia, for example medial nasal process (nasal septum) versus the mandibular primordia (Meckel's cartilage). The neural crest determines the shape of the face, that is characteristic species shape. These effects are mediated, in part, by BMP4 expression and the positioning of the FEZ, a growth zone in the upper face. The cranial mesoderm and cranial NCC are required for both the development of the head and heart and therefore, cardiac and craniofacial abnormalities often occur together. The development of some cardiac muscles and cranial striated muscles has shared molecular requirements.

Facial shape and allometry quantitative trait locus intervals in the Diversity Outbred mouse are enriched for known skeletal and facial development genes

“…Structured differences (covariance) in facial shape, and between facial shape and size, depend upon variation in the biological processes that coordinate facial development [1][2][3][4][5][6][7]. Understanding how these processes act and combine to build a facial skeleton requires interrogation at multiple levels of the genotype-phenotype (GP) map [8,9]. Among the most fundamental of these inquiries is the search for genetic variants that contribute to facial shape variation.…”

Gene regulatory dynamics during craniofacial development in a carnivorous marsupial

“…The vertebrate head is a highly complex region of the body that plays a key role in an organism's ecology by centralizing numerous structures involved in diet, sensory perception and behaviour [1]. Consequently, evolution has modified craniofacial development across lineages, producing a wide array of head morphologies concomitant with the diverse niches that vertebrates occupy.…”