Localization of cartilage linking protein 1 during primary neurulation in the chick embryo.

Primary neurulation is a form-shaping event during the early development of the vertebrate embryo in which the neural plate is rolled up into the neural tube, the rudiment of the central nervous system. In an effort to identify genes specifically expressed in tissues lateral to the chick neural plate--tissues known to generate extrinsic forces for primary neurulation--we designed a subtractive scheme and identified a positive clone as the gene encoding chick cartilage linking protein 1 (CRTL1). CRTL1 (also known as link protein) is a small glycoprotein of the extracellular matrix that was originally identified for its role in stabilizing aggregates of aggrecan and hyaluronan in cartilage. In addition to being expressed in cartilage, CRTL1 is also immunolocalized in several noncartilaginous tissues as assessed with the 4B6 monoclonal antibody. Using the 4B6 antibody and the G9 riboprobe derived from our subtraction, we report the detailed distribution of CRTL1 protein and crtl1 transcripts during primary neurulation in chick embryos. This report emphasizes and briefly discusses important differences between the RNA expression pattern and the domains of accumulation of the protein. CRTL1 prominently accumulates in the basal lamina of the epidermal ectoderm just lateral to the neural plate. Based on the crucial role of the interface between this tissue and the neuroepithelium in the formation of the neural folds, and because of the biophysical role of hyaluronan in tissue morphogenesis, we propose that crtl1 represents is an excellent candidate neurulation gene, worthy of further study.