Choanal atresia and stenosis: Development and diseases of the nasal cavity

Focus Article

Hiroshi Kurosaka

Published Online: Oct 15 2018

DOI: 10.1002/wdev.336

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Proper craniofacial development in vertebrates depends on growth and fusion of the facial processes during embryogenesis. Failure of any step in this process could lead to craniofacial anomalies such as facial clefting, which has been well studied with regard to its molecular etiology and cellular pathogenesis. Nasal cavity invagination is also a critical event in proper craniofacial development, and is required for the formation of a functional nasal cavity and airway. The nasal cavity must connect the nasopharynx with the primitive choanae to complete an airway from the nostril to the nasopharynx. In contrast to orofacial clefts, defects in nasal cavity and airway formation, such as choanal atresia (CA), in which the connection between the nasal airway and nasopharynx is physically blocked, have largely been understudied. This is also true for a narrowed connection between the nasal cavity and the nasopharynx, which is known as choanal stenosis (CS). CA occurs in approximately 1 in 5,000 live births, and can present in isolation but typically arises as part of a syndrome. Despite the fact that CA and CS usually require immediate intervention, and substantially affect the quality of life of affected individuals, the etiology and pathogenesis of CA and CS have remained elusive. In this review I focus on the process of nasal cavity development with respect to forming a functional airway and discuss the cellular behavior and molecular networks governing this process. Additionally, the etiology of human CA is discussed using examples of disorders which involve CA or CS. This article is categorized under: Signaling Pathways > Cell Fate Signaling Comparative Development and Evolution > Model Systems Birth Defects > Craniofacial and Nervous System Anomalies

Invagination of nasal and oral epithelium takes place during embryonic craniofacial development. (a) Oblique view of developing mouse head with whole mount nuclear fluorescent imaging at E11.0, E11.5, and E12.0, which was modified from reference (Kurosaka, ). Yellow color indicates the level of frontal section shown in (b). Red lines indicate the position where the facial processes fuse. (b–d) schematic drawing of nasal (pink) and oral epithelium (light blue) during the process of nasal fin, oronasal membrane and primitive choana formation. Green color in (c) indicates the level of section which is shown in (d). (d) Sagittal view of the process of primitive choana development. The drawings in (b–d) represent one‐half of the nasal area. LNP, Lateral nasal process; MNP, Medial nasal process; MXP, Maxillary process; MAN, Mandible; NC, Nasal cavity

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Expression pattern of RARE‐LacZ reporter and retinoic acid signaling‐related genes during choana development. Intra‐oral view of maxillary complex at E11.5 (a) and E12.5 (f) using whole‐mount nuclear fluorescent imaging. (b and g) LacZ‐stained RARE‐LacZ embryo's maxilla. (c–e and h–j) whole‐mount in situ hybridization of genes indicated at the top. Scale bar: 500 μm

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Schematic drawing of the process of nasal septum and secondary palate fusion. The two figures represent the frontal plane of the maxilla from E13.5 to 14.5. Pink and light blue color indicate nasal epithelium and oral epithelium, respectively. Red arrows indicate the direction of growth of nasal septum (NS) and secondary palatal shelf (PS). By the fusion of palatal shelves and nasal septum, the nasal cavity (NC) becomes completely separate from the oral cavity. NC, Nasal cavity; NS, Nasal septum; PS, Palatal shelf

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