Diversification of behavior and postsynaptic properties by netrin-G presynaptic adhesion family proteins.

Background: Vertebrate-specific neuronal genes are expected to play a critical role in the diversification and evolution of higher brain functions. Among them, the glycosylphosphatidylinositol (GPI)-anchored netrin-G subfamily members in the UNC6/netrin family are unique in their differential expression patterns in many neuronal circuits, and differential binding ability to their cognate homologous post-synaptic receptors.

Results: To gain insight into the roles of these genes in higher brain functions, we performed comprehensive behavioral batteries using netrin-G knockout mice.

Netrin-G/NGL complexes encode functional synaptic diversification.

Synaptic cell adhesion molecules are increasingly gaining attention for conferring specific properties to individual synapses. Netrin-G1 and netrin-G2 are trans-synaptic adhesion molecules that distribute on distinct axons, and their presence restricts the expression of their cognate receptors, NGL1 and NGL2, respectively, to specific subdendritic segments of target neurons. However, the neural circuits and functional roles of netrin-G isoform complexes remain unclear.

Regulatory factor X transcription factors control Musashi1 transcription in mouse neural stem/progenitor cells.

The transcriptional regulation of neural stem/progenitor cells (NS/PCs) is of great interest in neural development and stem cell biology. The RNA-binding protein Musashi1 (Msi1), which is often employed as a marker for NS/PCs, regulates Notch signaling to maintain NS/PCs in undifferentiated states by the translational repression of Numb expression. Considering these critical roles of Msi1 in the maintenance of NS/PCs, it is extremely important to elucidate the regulatory mechanisms by which Msi1 is selectively expressed in these cells.

Identification of transcriptional regulatory elements for Ntng1 and Ntng2 genes in mice.

Background: Higher brain function is supported by the precise temporal and spatial regulation of thousands of genes. The mechanisms that underlie transcriptional regulation in the brain, however, remain unclear. The Ntng1 and Ntng2 genes, encoding axonal membrane adhesion proteins netrin-G1 and netrin-G2, respectively, are paralogs that have evolved in vertebrates and are expressed in distinct neuronal subsets in a complementary manner.

Hippocampal CA3 and CA2 have distinct bilateral innervation patterns to CA1 in rodents.

Ipsilateral and contralateral hippocampal CA3-CA1 and CA2-CA1 projections were investigated in adult male Long-Evans rats by retrograde tracing. Injection of the retrograde tracer cholera toxin subunit B in the strata oriens and radiatum of dorsal CA1 resulted in labeling of predominantly pyramidal cells in ipsilateral and contralateral CA3 and CA2. The contralateral and ipsilateral anterior-posterior extents of CA3 innervation to CA1 were similar.

Identification of a novel intronic enhancer responsible for the transcriptional regulation of musashi1 in neural stem/progenitor cells.

Background: The specific genetic regulation of neural primordial cell determination is of great interest in stem cell biology. The Musashi1 (Msi1) protein, which belongs to an evolutionarily conserved family of RNA-binding proteins, is a marker for neural stem/progenitor cells (NS/PCs) in the embryonic and post-natal central nervous system (CNS). Msi1 regulates the translation of its downstream targets, including m-Numb and p21 mRNAs.