Expression and regulation of the Msx1 natural antisense transcript during development

Bidirectional transcription, leading to the expression of an antisense (AS) RNA partially complementary to the protein coding sense (S) RNA, is an emerging subject in mammals and has been associated with various processes such as RNA interference, imprinting and transcription inhibition. Homeobox genes do not escape this bidirectional transcription, raising the possibility that such AS transcription occurs during embryonic development and may be involved in the complexity of regulation of homeobox gene expression. According to the importance of the Msx1 homeobox gene function in craniofacial development, especially in tooth development, the expression and regulation of its recently identified AS transcripts were investigated in vivo in mouse from E9.5 embryo to newborn, and compared with the S transcript and the encoded protein expression pattern and regulation. The spatial and temporal expression patterns of S, AS transcripts and protein are consistent with a role of AS RNA in the regulation of Msx1 expression in timely controlled developmental sites. Epithelial–mesenchymal interactions were shown to control the spatial organization of S and also AS RNA expression during early patterning of incisors and molars in the odontogenic mesenchyme. To conclude, this study clearly identifies the Msx1 AS RNA involvement during tooth development and evidences a new degree of complexity in craniofacial developmental biology: the implication of endogenous AS RNAs

Osteopetrosis and Its Relevance for the Discovery of New Functions Associated with the Skeleton

Osteopetrosis is a rare genetic disorder characterized by an increase of bone mass due to defective osteoclast function. Patients typically displayed spontaneous fractures, anemia, and in the most severe forms hepatosplenomegaly and compression of cranial facial nerves leading to deafness and blindness. Osteopetrosis comprises a heterogeneous group of diseases as several forms are known with different models of inheritance and severity from asymptomatic to lethal. This review summarizes the genetic and clinical features of osteopetrosis, emphasizing how recent studies of this disease have contributed to understanding the central role of the skeleton in the whole body physiology. In particular, the interplay of bone with the stomach, insulin metabolism, male fertility, the immune system, bone marrow, and fat is described