Copper-catalyzed intermolecular formal (5 + 1) annulation of 1,5-diynes with 1,2,5-oxadiazoles.

One-carbon homologation reactions based on one-carbon insertion into the N-O bond of heterocycles have received tremendous interest over the past decades. However, these protocols have to rely on the use of hazardous and not easily accessible diazo compounds as precursors, and examples of the relevant asymmetric catalysis have not been reported. Here we show that a copper-catalyzed intermolecular formal (5 + 1) annulation of 1,5-diynes with 1,2,5-oxadiazoles involving one-carbon insertion into the heterocyclic N-O bond via non-diazo approach.

Global Quantitative Proteomics Analysis Reveals the Downstream Signaling Networks of Msx1 and Msx2 in Myoblast Differentiation.

Unlabelled: The msh homeobox 1 (Msx1) and msh homeobox 2 (Msx2) coordinate in myoblast differentiation and also contribute to muscle defects if altered during development. Deciphering the downstream signaling networks of Msx1 and Msx2 in myoblast differentiation will help us to understand the molecular events that contribute to muscle defects. Here, the proteomics characteristics in Msx1- and Msx2-mediated myoblast differentiation was evaluated  using isobaric tags for the relative and absolute quantification labeling technique (iTRAQ).

An intellectual disability-related MED23 mutation dysregulates gene expression by altering chromatin conformation and enhancer activities.

Transcriptional Mediator controls diverse gene programs for various developmental and pathological processes. The human Mediator MED23/R617Q mutation was reported in a familial intellectual disability (ID) disorder, although the underlying mechanisms remain poorly understood. Constructed by gene editing, the Med23/R617Q knock-in mutant mice exhibited embryonic lethality due to the largely reduced Med23/R617Q protein level, but the R617Q mutation in HEK293T cells didn't change its expression and incorporation into Mediator Complex.

Med23 supports angiogenesis and maintains vascular integrity through negative regulation of angiopoietin2 expression.

The mammalian Mediator complex consists of over 30 subunits and functions as a transcriptional hub integrating signaling for tissue-specific gene expression. Although the role of the Mediator complex in transcription has been extensively investigated, the functions of distinct Mediator subunits in development are not well understood. Here, we dissected the role of the Mediator subunit Med23 in mouse cardiovascular development.

Msx1 cooperates with Runx1 for inhibiting myoblast differentiation.

Myogenesis is an important and complicated biological process, especially during the process of embryonic development. The homeoprotein Msx1 is a crucial transcriptional repressor of myogenesis and maintains myogenic precursor cells in an undifferentiated, proliferative state. However, the molecular mechanism through which Msx1 coordinates myogenesis remains to be elucidated.

Phosphorylation of Msx1 promotes cell proliferation through the Fgf9/18-MAPK signaling pathway during embryonic limb development.

Msh homeobox (Msx) is a subclass of homeobox transcriptional regulators that control cell lineage development, including the early stage of vertebrate limb development, although the underlying mechanisms are not clear. Here, we demonstrate that Msx1 promotes the proliferation of myoblasts and mesenchymal stem cells (MSCs) by enhancing mitogen-activated protein kinase (MAPK) signaling. Msx1 directly binds to and upregulates the expression of fibroblast growth factor 9 (Fgf9) and Fgf18.

Loss of homeoprotein Msx1 and Msx2 leading to athletic and kinematic impairment related to the increasing neural excitability of neurons in aberrant neocortex in mice.

Although homeoproteins Msx1 and Msx2, the cell-specific transcription regulators, have been proven to play multiple roles in the embryogenesis of bone, muscle and tooth, the functions and mechanisms of Msx1 and Msx2 in the development of the central nervous system of mice after birth are not clear because of the death of Msx1 and Msx1/2 germline-deleted embryo at late gestation of mouse. In current research, Nestin-Cre mice was introduced to generate the central nervous system-specific knockout mice (Nestin-Cre;Msx1,Msx2). We found that besides the falling of the body mass and the brain volume, the cortical tissue sections and staining showed the decreasing thickness of layer II-IV and declining number of vertebral cells in layer V resulting from Msx1/2 deletion.

L-periaxin interacts with S-periaxin through its PDZ domain.

Periaxin was first identified as a protein in myelinating Schwann cells through a screen of novel cytoskeleton-associated proteins in peripheral nerve myelination. The periaxin gene encodes two isoforms, namely, L- and S-periaxin, which are 1461 and 147 residues in size, respectively. Several loss-of-function mutations linked to autosomal recessive Dejerine-Sottas neuropathy and demyelinating Charcot-Marie-Tooth disease in periaxin have been described.