Cleft Candidate Genes and Their Products in Human Unilateral Cleft Lip Tissue.

Mārtiņš Vaivads,Ilze Akota,Māra Pilmane

doi:10.3390/diseases9020026

Abstract

Cleft lip and palate are common congenital pathologies that affect the human population worldwide. The formation of cleft lip is associated with multiple genes and their coded proteins, which regulate the development of craniofacial region, but the exact role of these factors is not always clear. The use of morphological studies for evaluation of human cleft-affected tissue has been limited because of insufficiency of available pathological material. The aim of this study was to detect and compare the immunohistochemical expression of cleft candidate gene coded proteins (DLX4, MSX2, HOXB3, SHH, PAX7, SOX3, WNT3A, and FOXE1) in the non-syndromic unilateral cleft lip patient tissue and control group tissue. A semiquantitative counting method was used to evaluate the tissue in biotin-streptavidin-stained slides. Statistically significant differences between the patient and control groups were found for the number of immunoreactive structures for SHH (p = 0.019) and FOXE1 (p = 0.011) in the connective tissue and SOX3 (p = 0.012) in the epithelium. Multiple statistically significant very strong and strong correlations were found between the immunoreactives in cleft-affected tissue. These significant differences and various correlations indicate that multiple morphopathogenetic pathways are possibly involved in unilateral cleft lip pathogenesis. Therefore, we further discuss these possible interactions.

Highlights

Cleft lip and palate are one of the most common congenital pathologies in the human population
Strong correlation was seen between the number of Homeobox B3 (HOXB3) positive cells in the patient connective tissue and the number of SRY-Box Transcription Factor 3 (SOX3) positive cells in the patient epithelium (Spearman’s rho = 0.817, p = 0.004), between the number of HOXB3 positive cells in the patient epithelium and the number of Paired box 7 (PAX7) positive cells in the patient epithelium (Spearman’s rho = 0.677, p = 0.032) and between the number of DLX4 positive cells in the Diseases 2021, 9, x FOR PEER REVIEWpatient epithelium and the number of WNTA3A positive cells in the patient epithe8liouf 1m6 (Spearman’s rho = 0.660, p = 0.038) (Table 4)
After evaluation of cleft affected tissues, a statistically significant increase in the number of sonic hedgehog (SHH) positive structures was observed in patient connective tissue compared to the control group, which may indicate the possible role of SHH in formation of cleft lip

Summary

Introduction

Cleft lip and palate are one of the most common congenital pathologies in the human population. Non-syndromic cleft lip and palate pathogenesis involves the dysregulated expression of multiple genes. These genes play an important role in regulating the development of the craniofacial region. Dysregulation of these genes is associated with the development of craniofacial clefts but the exact mechanisms are not always clearly known. These genes and their coded proteins have been studied by mostly using animal models but studies on human cleft tissues are limited because of ethical concerns and the lack of available material [2]

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