Dynamic expression patterns of leucine-rich repeat containing protein 10 in the heart.

Leucine-rich repeat containing protein 10 (LRRC10) is a heart-specific factor whose function remains unknown. Examination of the intracellular location of the gene products is a critical step in determining the biological functions of the protein. Our expression analyses in mice indicate that LRRC10 is exclusively expressed from the precardiac region in early embryos to the adult heart. LRRC10 expression is markedly elevated upon birth, suggesting its role in the embryonic as well as adult hearts. Of interest, LRRC10 exhibits dynamic intracellular expression patterns in cardiomyocytes. Cardiomyocytes from embryos and newborns show diffuse cytoplasmic and nuclear staining of LRRC10. In contrast, striking striations are observed in adult cardiomyocytes, which are colocalized with the markers for the Z-line, sarcoplasmic reticulum (SR), and transverse (T)-tubule by double immunostaining. Further investigation by electron micrographs places LRRC10 in a diad region where the SR interacts with the T-tubule that locates along the Z-line.

Mammalian DSCAMs: roles in the development of the spinal cord, cortex, and cerebellum?

Central nervous system (CNS) development involves neural patterning, neuronal and axonal migrations, and synapse formation. DSCAM, a chromosome 21 axon guidance molecule, is expressed by CNS neurons during development and throughout adult life. We now report that DSCAM and its chromosome 11 paralog DSCAML1 exhibit inverse ventral-dorsal expression patterns in the developing spinal cord and distinct, partly inverse, expression patterns in the developing cortex, beginning in the Cajal-Retzius cells. In the adult cortex, DSCAM predominates in layer 3/5 pyramidal cells and DSCAML1 predominates in layer 2 granule cells. In the cerebellum, DSCAM is stronger in the Purkinje cells and DSCAML1 in the granule cells. Finally, we find that the predicted DSCAML1 protein contains 60 additional N-terminal amino acids which may contribute to its distinct expression pattern and putative function. We propose that the DSCAMs comprise novel elements of the pathways mediating dorsal-ventral patterning and cell-fate specification in the developing CNS.

The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation.

The Ezh2 protein endows the Polycomb PRC2 and PRC3 complexes with histone lysine methyltransferase (HKMT) activity that is associated with transcriptional repression. We report that Ezh2 expression was developmentally regulated in the myotome compartment of mouse somites and that its down-regulation coincided with activation of muscle gene expression and differentiation of satellite-cell-derived myoblasts. Increased Ezh2 expression inhibited muscle differentiation, and this property was conferred by its SET domain, required for the HKMT activity. In undifferentiated myoblasts, endogenous Ezh2 was associated with the transcriptional regulator YY1. Both Ezh2 and YY1 were detected, with the deacetylase HDAC1, at genomic regions of silent muscle-specific genes. Their presence correlated with methylation of K27 of histone H3. YY1 was required for Ezh2 binding because RNA interference of YY1 abrogated chromatin recruitment of Ezh2 and prevented H3-K27 methylation. Upon gene activation, Ezh2, HDAC1, and YY1 dissociated from muscle loci, H3-K27 became hypomethylated and MyoD and SRF were recruited to the chromatin. These findings suggest the existence of a two-step activation mechanism whereby removal of H3-K27 methylation, conferred by an active Ezh2-containing protein complex, followed by recruitment of positive transcriptional regulators at discrete genomic loci are required to promote muscle gene expression and cell differentiation.