PCNS: A novel protocadherin required for cranial neural crest migration and somite morphogenesis in Xenopus

Abstract

Protocadherins (Pcdhs), a major subfamily of cadherins, play an important role in specific intercellular interactions in development. These molecules are characterized by their unique extracellular domain (EC) with more than 5 cadherin-like repeats, a transmembrane domain (TM) and a variable cytoplasmic domain. PCNS (Protocadherin in Neural crest and Somites), a novel Pcdh in Xenopus, is initially expressed in the mesoderm during gastrulation, followed by expression in the cranial neural crest (CNC) and somites. PCNS has 65% amino acid identity to Xenopus paraxial protocadherin (PAPC) and 42-49% amino acid identity to Pcdh 8 in human, mouse, and zebrafish genomes. Overexpression of PCNS resulted in gastrulation failure but conferred little if any specific adhesion on ectodermal cells. Loss of function accomplished independently with two non-overlapping antisense morpholino oligonucleotides resulted in failure of CNC migration, leading to severe defects in the craniofacial skeleton. Somites and axial muscles also failed to undergo normal morphogenesis in these embryos. Thus, PCNS has essential functions in these two important developmental processes in Xenopus.

Inca: a novel p21-activated kinase-associated protein required for cranial neural crest development

“…Our screen for Tfap2a targets has also yielded a novel protocadherin, named PCNS, that is required for NC migration (Rangarajan et al, 2006), and a surprisingly high proportion of epidermal genes also expressed in the NC (Luo et al, 2005). From these results and earlier work, a picture emerges in which Tfap2a…”

Ror2 signaling is required for local upregulation of GDF6 and activation of BMP signaling at the neural plate border

“…In our previous work, we have demonstrated that Wnt5a/Ror2 signaling is essential for the upregulation of paraxial protocadherin (Papc) in gastrulating embryos and that Papc acts as a positive modulator of Wnt/PCP signaling (Schambony and Wedlich, 2007;Unterseher et al, 2004). Accordingly, we co-injected papc RNA or an RNA encoding the related and functionally redundant ectodermal protocadherin Pcns (Rangarajan et al, 2006;Schneider et al, 2014) to restore Wnt/PCP signaling in Ror2 morphant embryos. Indeed, expressing either Papc or Pcns was sufficient to rescue gdf6 expression in Ror2 deficient embryos (Fig.…”

Mechanisms driving neural crest induction and migration in the zebrafish andXenopus laevis

“…22,160 The predominant cadherin in the early Xenopus embryo is C-cadherin; 162 beginning in the late blastula an E-cadherin-like molecule is expressed in the developing epidermis and is absent from the developing neural plate. 163,164 Beginning at gastrulation, cadherin-11 is expressed in a Wnt-dependent manner; 165 later it is expressed in migrating neural crest cells, 166 together with the protocadherin PCNS 167 and N-cadherin. 168 Functional studies of cadherin-11 indicate that its overexpression, or the overexpression of a mutant polypeptide missing its cytoplasmic b-catenin binding domain, blocks cranial neural crest migration and leads to their neural differentiation.…”