ABSTRACT
Extracellular matrix (ECM) proteins play an important role in early cortical development, specifically in the formation of neural connections and in controlling the cyto-architecture of the central nervous system. F-spondin and Mindin are a family of matrix-attached adhesion molecules that share structural similarities and overlapping domains of expression. Genes for both proteins contain a thrombospondin type I repeat(s) at the C terminus and an FS1-FS2 (spondin) domain. Both the vertebrate F-spondin and the zebrafish mindins are expressed on the embryonic floor plate. In the current study we have cloned the rat homologue of mindin and studied its expression and activity together with F-spondin in the developing rodent brain. The two genes are abundantly expressed in the developing hippocampus. In vitro studies indicate that both F-spondin and Mindin promote adhesion and outgrowth of hippocampal embryonic neurons. We have also demonstrated that the two proteins bind to a putative receptor(s) expressed on both hippocampal and sensory neurons.
Subject(s)
Extracellular Matrix Proteins/genetics , Gene Expression Regulation, Developmental , Growth Substances , Hippocampus/embryology , Neural Cell Adhesion Molecules/genetics , Neurons/physiology , Peptides , Zebrafish Proteins , Amino Acid Sequence , Animals , Cloning, Molecular , Drosophila , Drosophila Proteins , Extracellular Matrix Proteins/chemistry , Extracellular Matrix Proteins/physiology , Intercellular Signaling Peptides and Proteins , Membrane Proteins , Molecular Sequence Data , Neural Cell Adhesion Molecules/chemistry , Neural Cell Adhesion Molecules/physiology , Organ Specificity , RNA, Messenger/analysis , RNA, Messenger/genetics , Rats , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Repetitive Sequences, Amino Acid , Sequence Alignment , Sequence Homology, Amino Acid , Transcription, Genetic , ZebrafishABSTRACT
The commissural axons project toward and across the floor plate. They then turn into the longitudinal axis, extending along the contralateral side of the floor plate. F-spondin, a protein produced and secreted by the floor plate, promotes adhesion and neurite extension of commissural neurons in vitro. Injection of purified F-spondin protein into the lumen of the spinal cord of chicken embryos in ovo resulted in longitudinal turning of commissural axons before reaching the floor plate, whereas neutralizing antibody (Ab) injections caused lateral turning at the contralateral floor plate boundary. These combined in vitro and in vivo results suggest that F-spondin is required to prevent the lateral drifting of the commissural axons after having crossed the floor plate.
