Roles of Wnt Signaling Pathway and ROR2 Receptor in Embryonic Development: An Update Review Article

Abstract

The Wnt family is a large class of highly conserved cysteine-rich secretory glycoproteins that play a vital role in various cellular and physiological courses through different signaling pathways during embryogenesis and tissue homeostasis 3. Wnt5a is a secreted glycoprotein that belongs to the noncanonical Wnt family and is involved in a wide range of developmental and tissue homeostasis. A growing body of evidence suggests that Wnt5a affects embryonic development, signaling through various receptors, starting with the activation of β-catenin by Wnt5a. In addition to affecting planar cell polarity and Ca2+ pathways, β-catenin also includes multiple signaling cascades that regulate various cell functions. Secondly, Wnt5a can bind to Ror receptors to mediate noncanonical Wnt signaling and a significant ligand for Ror2 in vertebrates. Consistent with the multiple functions of Wnt5A/Ror2 signaling, Wnt5A knockout mice exhibited various phenotypic defects, including an inability to extend the anterior and posterior axes of the embryo. Numerous essential roles of Wnt5a/Ror2 in development have been demonstrated. Therefore, Ror signaling pathway become a necessary target for diagnosing and treating human diseases. The Wnt5a- Ror2 signaling pathway as a critical factor has attracted extensive attention.

ROR2 deficit may induce the tetralogy of Fallot via down‐regulating of β‐catenin/SOX3/HSPA6 in vitro and in vivo

“…Tetralogy of Fallot is one of the most common congenital heart diseases developed during embryonic development. In embryonic development, successful cell‐to‐cell coordination is required to provide appropriate direction, resulting in cell proliferation, differentiation and apoptosis 9 . Right ventricular hypertrophy is a secondary process resulting from the hemodynamic overload proper of the malformation.…”

“…However, their role is unspecific and not limited to septum formation 25–28 . In addition, other studies have shown that ROR2 is essential for maintaining cardiomyocyte proliferation 9,29 . Besides that, ROR2 appears to play a dual role as a tumour suppressor or activator in certain types of cancer 30 .…”

“…Recent studies have identified receptor tyrosine kinase‐like orphan receptor (ROR2) as a novel therapeutic and diagnostic target 7,8 . ROR2 is a member of the RTK superfamily of surface receptors and may play an integral role in the normal development of cardiac tissue 9–13 . Besides, studies have shown that ROR2 is required for embryonic cardiac development, including septal formation 9,14 .…”

“…7,8 ROR2 is a member of the RTK superfamily of surface receptors and may play an integral role in the normal development of cardiac tissue. [9][10][11][12][13] Besides, studies have shown that ROR2 is required for embryonic cardiac development, including septal formation. 9,14 ROR and Frizzled receptors also mediate the Wnt/β-catenin-independent signalling.…”

Downregulation of ROR2 attenuates LPS‐induced A549 cell injury through JNK and ERK signaling pathways

“…Receptor tyrosine kinase‐like orphan receptor 2 (ROR2), encoding an orphan receptor tyrosine kinase, is selectively expressed in specific cell lineages, which plays critical roles in regulating cell cycle, migration, proliferation, and apoptosis as well as inflammatory responses by initiating signaling cascades. 7 , 8 ROR2 is an important receptor involved in the Wnt5a‐mediated inflammatory response in atherosclerosis 9 and PM2.5‐related chronic obstructive pulmonary disease 10 as well as the malignancies. 11 Extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) are important regulatory proteins in the inflammatory responses of LPS‐induced ALI.…”