Neurocan developmental expression and function during early avian embryogenesis

Abstract

Background: Neurocan is the most abundant lectican considered to be expressed exclusively in the central nervous system. Neurocan interacts with other matrix components, with cell adhesion molecules, growth factors, enzymes and cell surface receptors. The interaction repertoire and evidence from cellular studies indicated an active role in signal transduction and major cellular programs. Relatively little is known about the neurocan tissue-specific distribution and function during embryonic development. This study examined the time of appearance and subsequent spatio-temporal expression pattern of neurocan and its functional activities during the earliest stages of development in the chick embryo. Methods: To detect the first expression and spatio-temporal distribution of neurocan in the early embryo, strand-specific reverse transcription-polymerase chain reaction (RT-PCR), immunoprecipitation and immunofluorescence were performed. An anti-neurocan blocking antibody transient pulse was applied to embryos at the onset of the neurula stage to perturb neurocan activities in the background of the current cellular signaling state of the developing embryo. Results: Neurocan was first detected in the inchoate neural plate and the extracellular matrix in embryos at the definitive streak stage (late gastrula). During early organogenesis, neurocan fluorescence was very intense in the neural tube, notochord, neural crest cells, pharyngeal arches, foregut lower wall, presumptive pronephric tubules, blood islands, dorsal mesocardium, intense in myocardium and distinct in endocardium, very intense in the presumptive cornea and intense in retina and lens, intense in somite and nephrotome. Antibody perturbation of neurocan function resulted in three predominant defects: (1) abnormal expansion of neuroepithelium in the surface ectoderm flanking the neural tube; (2) neural crest cells formed epithelial pockets located on the ectoderm apical surface; and (3) surface ectoderm cells (presumptive epidermis) acquired mesenchymal cell properties, invaded into the subectodermal space and interacted with neuroectoderm. Conclusions: Neurocan was first expressed in the inchoate neural plate at the late gastrula stage. Neurocan expression was very intense in the developing central nervous system as well as in many non-neural tissues. Neurocan seems to modulate signalling in the neural-non-neural tissue specification and the adhesive and signalling activities of epithelial-mesenchymal cells and neural crest cell motility in the early embryo.

Lamprey lecticans link new vertebrate genes to the origin and elaboration of vertebrate tissues

“…To what degree these differences reflect divergence in lectican regulation between lamprey and gnathostomes, or the incomplete documentation of lectican expression in gnathostomes, is unclear. In the central nervous system, lecA and frog vcan both display expression in the neural [38,46,47]. Although lectican expression in the forming nervous system appears to conserved among living vertebrates, the role of lecticans in neural development is unclear, as bcan and ncan-deficient mice show only minor differences in neuron function [56,57].…”

“…vcan is the most widely expressed lectican and is transcribed in mesoderm-derived tissues and organs including the kidneys, heart, muscles, and skeleton [29][30][31][32][33][34], and various neurectodermal derivatives like the otic vesicle, lens primordium [32], oligodendrocytes, Schwann Cells, the perineuronal net, ectodermal placodes, and migrating neural crest cells [20,28,[35][36][37][38]. bcan and ncan are primarily expressed in the nervous system [20,26,[39][40][41][42][43][44][45][46][47][48][49], though notochord and heart expression has also been reported [46,[50][51][52]. Of the four lecticans, mutation of acan leads to the most significant defects, including severe chondrodysplasia [23], while vcan loss-of-function causes abnormal eye and heart development [53][54][55].…”

Lamprey Lecticans Link New Vertebrate Genes to the Origin and Elaboration of Vertebrate Tissues

“…As in the forming nervous system lectican expression in mesodermal derivatives is largely conserved between lamprey and gnathostomes. In the gnathostome heart, aggrecan marks migratory cardiac mesoderm [29], while ncan marks the forming myocardium and splanchnic mesoderm, and vcan marks the endocardium and the heart tube [29,46,51,82]. In lamprey, lecA is expressed in the myocardium [ Fig 3E''] while lecD marks the posterior endocardium and heart tube as well as the ventral aorta [ Fig 6D'].…”

“…vcan is the most widely expressed lectican and is transcribed in mesoderm-derived tissues and organs including the kidneys, heart, muscles, and skeleton [29][30][31][32][33][34], and various neurectodermal derivatives like the otic vesicle, lens primordium [32], oligodendrocytes, Schwann Cells, the perineuronal net, ectodermal placodes, and migrating neural crest cells [20,28,[35][36][37][38]. bcan and ncan are primarily expressed in the nervous system [20,26,[39][40][41][42][43][44][45][46][47][48][49], though notochord and heart expression has also been reported [46,[50][51][52]. Of the four lecticans, mutation of acan leads to the most significant defects, including severe chondrodysplasia [23], while vcan loss-of-function causes abnormal eye and heart development [53][54][55].…”

“…lecA and lecB are expressed in the developing brain like bcan and ncan [Fig 3D', D'', Fig 4D'], though not as broadly. Like ncan, bcan, and vcan, lecA and lecB are expressed in the cranial placodes and sensory ganglia [Fig 3D', D'', Fig 4D'], though in different neural populations[38,46,47]. Although lectican expression in the forming nervous system appears to conserved among living vertebrates, the role of lecticans in neural development is unclear, as bcan and ncan-deficient mice show only minor differences in neuron function[56,57].…”