Disruption of BMP4 signaling is associated with laryngeal birth defects in a mouse model

Abstract

Laryngeal birth defects are considered rare, but they can be life-threatening conditions. The BMP4 gene plays an important role in organ development and tissue remodeling throughout life. Here we examined its role in laryngeal development complementing similar efforts for the lung, pharynx, and cranial base. Our goal was to determine how different imaging techniques contribute to a better understanding of the embryonic anatomy of the normal and diseased larynx in small specimens. Contrast-enhanced micro CT images of embryonic larynx tissue from a mouse model with Bmp4 deletion informed by histology and whole-mount immunofluorescence were used to reconstruct the laryngeal cartilaginous framework in three dimensions. Laryngeal defects included laryngeal cleft, laryngeal asymmetry, ankylosis and atresia. Results implicate BMP4 in laryngeal development and show that the 3D reconstruction of laryngeal elements provides a powerful approach to visualize laryngeal defects and thereby overcoming shortcomings of 2D histological sectioning and whole mount immunofluorescence.