ACAM, a novel member of the neural IgCAM family, mediates anterior neural tube closure in a primitive chordate

Abstract

The neural IgCAM family of cell adhesion molecules, which includes NCAM and related molecules, has evolved via gene duplication and alternative splicing to allow for a wide range of isoforms with distinct functions and homophilic binding properties. A search for neural IgCAMs in ascidians (Ciona intestinalis, Ciona savignyi, and Phallusia mammillata) has identified a novel set of truncated family members that, unlike the known members, lack fibronectin III domains and consist of only repeated Ig domains. Within the tunicates this form appears to be unique to the ascidians, and it was designated ACAM, for Ascidian Cell Adhesion Molecule. In C. intestinalis ACAM is expressed in the developing neural plate and neural tube, with strongest expression in the anterior sensory vesicle precursor. Unlike the two other conventional neural IgCAMs in C. intestinalis, which are expressed maternally and throughout the morula and blastula stages, ACAM expression initiates at the gastrula stage. Moreover, C. intestinalis ACAM is a target of the homeodomain transcription factor OTX, which plays an essential role in the development of the anterior central nervous system. Morpholino (MO) knockdown shows that ACAM is required for neural tube closure. In MO-injected embryos neural tube closure was normal caudally, but the anterior neuropore remained open. A similar phenotype was seen with overexpression of a secreted version of ACAM. The presence of ACAM in ascidians highlights the diversity of this gene family in morphogenesis and neurodevelopment.

The central nervous system of ascidian larvae

“…Interestingly, while the posterior neural tube uses a zippering mechanism to close, the anterior neural tube closure appears to follow a ‘purse string’ contraction . Anterior neural tube closure has not been studied in detail in Ciona , though it appears to depend upon ascidian cell adhesion molecule (ACAM) . Sealing of the anterior neural folds at the end of neurulation depends upon T‐type calcium channels and downregulation of ephrin‐Eph signaling, though the exact mechanism is not understood .…”

“…94 Anterior neural tube closure has not been studied in detail in Ciona, though it appears to depend upon ascidian cell adhesion molecule (ACAM). 135 Sealing of the anterior neural folds at the end of neurulation depends upon T-type calcium channels and downregulation of ephrin-Eph signaling, though the exact mechanism is not understood. 136 An anion transporter, soluble carrier 26 (Slc26aα), and an ammonium transport protein (ATM1a) are required for the correct formation of the lumen of the sensory vesicle.…”