Cellular and developmental basis of orofacial clefts

Abstract

During craniofacial development, defective growth and fusion of the upper lip and/or palate can cause orofacial clefts (OFCs), which are among the most common structural birth defects in humans. The developmental basis of OFCs includes morphogenesis of the upper lip, primary palate, secondary palate, and other orofacial structures, each consisting of diverse cell types originating from all three germ layers: the ectoderm, mesoderm, and endoderm. Cranial neural crest cells and orofacial epithelial cells are two major cell types that interact with various cell lineages and play key roles in orofacial development. The cellular basis of OFCs involves defective execution in any one or several of the following processes: neural crest induction, epithelial‐mesenchymal transition, migration, proliferation, differentiation, apoptosis, primary cilia formation and its signaling transduction, epithelial seam formation and disappearance, periderm formation and peeling, convergence and extrusion of palatal epithelial seam cells, cell adhesion, cytoskeleton dynamics, and extracellular matrix function. The latest cellular and developmental findings may provide a basis for better understanding of the underlying genetic, epigenetic, environmental, and molecular mechanisms of OFCs.

Single cell transcriptomics and developmental trajectories of murine cranial neural crest cell fate determination and cell cycle progression

“…During mouse facial development, the morphogenesis of the LNP-and MNP-derived structures progresses from E10.5 to E12.5. However, MxP cells continue to grow until E15.5 to give rise to the secondary palate (Ji et al, 2020). This is consistent with our results that, at E11.5, LNP and MNP cells (m0, m1, and m2) were grouped into three clusters at different differential stages while most of the MxP cells (m3) are still at an early developmental stage.…”

“…Therefore, it can label these tissues and their progeny cells with green fluorescence. Since the cranial NC cells migrate to their target region around E8.5 and the generation of the facial prominences is completed by E12.5 (Ji et al, 2020), we collected eGFP positive cells from E9.5, E10.5, E11.5, and E12.5 embryos using fluorescence-activated cell sorting (Fig. 1B, C).…”

Identification of maternal serum biomarkers for prenatal diagnosis of nonsyndromic orofacial clefts

“…Defects in cytoskeleton dynamics are considered to be the cellular basis of NSOFC. 22 Qian et al showed that TPM1 encodes actin-binding proteins and is involved in cytoskeleton organization, and polymorphisms in this gene might contribute to the etiology of NSOFC. 23 Recent studies indicate that single nucleotide polymorphisms in KRT18, which encodes the type I intermediate filament chain keratin 18, are a genetic susceptibility locus for NSOFC.…”

“…Cytoskeleton organization plays an important role in the development of the lip and palate. Defects in cytoskeleton dynamics are considered to be the cellular basis of NSOFC 22 . Qian et al .…”

What’s Shape Got to Do With It? Examining the Relationship Between Facial Shape and Orofacial Clefting

“…For example, the primary deficiency may involve the fusion process. In such cases, the facial prominences may grow in a normal manner and make contact, but something interferes with the molecular machinery that drives tissue fusion (reviewed in Ji et al, 2020 ). However, another possibility is that the nascent facial prominences are not able to contact one another or meet too late for proper fusion to take place.…”