The BBSome is an octameric protein complex involved in Bardet-Biedl syndrome (BBS), a human pleiotropic, autosomal recessive condition. Patients with BBS display various clinical features including obesity, hypertension, and renal abnormalities. Association studies have also linked the BBS genes to hypertension and other cardiovascular risks in the general population. The BBSome was originally associated with the function of cilia, a highly specialized organelle that extend from the cell membrane of most vertebrate cells. However, subsequent studies have implicated the BBSome in the control of a myriad of other cellular processes not related to cilia including cell membrane localization of receptors and gene expression. The development of animal models of BBS such as mouse lines lacking various components of the BBSome and associated proteins has facilitated studying their role in the control of cardiovascular function and deciphering the pathophysiological mechanisms responsible for the cardiovascular aberrations associated with BBS. These studies revealed the importance of the neuronal, renal, vascular, and cardiac BBSome in the regulation of blood pressure, renal function, vascular reactivity, and cardiac development. The BBSome has also emerged as a critical regulator of key systems involved in cardiovascular control including the renin-angiotensin system. Better understanding of the influence of the BBSome on the molecular and physiological processes relevant to cardiovascular health and disease has the potential of identifying novel mechanisms underlying hypertension and other cardiovascular risks. 

BBSome: a New Player in Hypertension and Other Cardiovascular Risks

Periosteum is essential for bone regeneration and damage repair in mammals. Most species of deer family (Cervidae) develop two kinds of special periosteum, antler periosteum and pedicle periosteum, both supporting the complete regeneration of antler. Antler is the bone organ with the fastest growth rate in mammals. Along with the fast growth of antler, its external tissues such as blood vessels, nerves and the covering skin also grow rapidly. Currently, it is still unclear whether antler periosteum contributes to the fast growth of antler and how. It is also unclear why the regenerative capacity of antler periosteum is weaker than that of pedicle periosteum. In this study, the in vitro culture system for antler periosteal cells (AnPC) was constructed for the first time using the mid-beam antler periostea during antler fast-growth period. According to our results, the cultured AnPC expressed classical MSC markers, consistent with the pedicle periosteal stem cells (PPSC). However, the fluorescence intensities of the MSC markers on AnPC were significantly weaker than those on PPSC. In addition, AnPC showed much lower proliferation rates than PPSC. The proliferation rates of the AnPC also gradually decreased after successive passages, while the proliferation rates of the pedicle periosteal stem cells remained unchanged. These findings may partially explain the weaker regenerative capacity of antler periosteum. Further comparative global gene analysis revealed clearly the different gene expressed patterns between AnPC and PPSC. AnPC may mainly function on promoting angiogenesis, nerve growth and intramembrane bone formation during antler regeneration, whereas PPSC may primarily be involved in androgen signaling receptor pathway and PI3K-Akt signaling pathway and function on maintaining stem cell renewal.

Constructing the in vitro culture system of the sika deer (cervus nippon) antler periosteal cell to detect its function on antler regeneration.

The primary cilium (PC) has emerged as an indispensable cellular antenna essential for signal transduction of important cell signaling pathways. The rapid acquisition of knowledge about PC biology has raised attention to PC as a therapeutic target in some neurological and psychiatric diseases. However, the role of PC in oligodendrocytes and its participation in myelination/remyelination remain poorly understood. Oligodendrocyte precursor cells (OPCs) give rise to oligodendrocytes during central nervous system (CNS) development. In adult, a small percentage of OPCs remains as undifferentiated cells located sparsely in the different regions of the CNS. These cells can regenerate oligodendrocytes and participate to certain extent in remyelination. This study aims characterize PC in oligodendrocyte lineage cells during post-natal development and in a mouse model of demyelination/remyelination. We show heterogeneity in the frequency of cilium presence on OPCs, depending on culture conditions in vitro and cerebral regions in vivo during development and demyelination/remyelination. In vitro, Lithium chloride (LiCl), Forskolin and Chloral Hydrate differentially affect cilium, depending on culture environment and PC length correlates with the cell differentiation state. Beside the role of PC as a keeper of cell proliferation, our results suggest its involvement in myelination/remyelination.

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Oligodendroglial primary cilium heterogeneity during development and demyelination/remyelination

Bardet-Biedl syndrome protein 4 (BBS4) localization has been studied in human embryos/fetuses from Carnegie stage 15 to 37 gestational weeks in neurosensory organs and brain, underlying the major clinical signs of BBS. We observed a correlation between the differentiation of the neurosensory cells (hair cells, photoreceptors, olfactory neurons) and the presence of a punctate BBS4 immunostaining in their apical cytoplasm. In the brain, BBS4 was localized in oligodendrocytes and myelinated tracts. In individual myelinated fibers, BBS4 immunolabelling was discontinuous, predominantly at the periphery of the myelin sheath. BBS4 immunolabelling was confirmed in postnatal developing white matter tracts in mouse as well as in mouse oligodendrocytes cultures. In neuroblasts/neurons, BBS4 was only present in reelin-expressing Cajal-Retzius cells. Our results show that BBS4, a protein of the BBSome, has both basal body/ciliary localization in neurosensory organs but extra-ciliary localization in oligodendrocytes. The presence of BBS4 in developing oligodendrocytes and myelin described in the present paper might attribute a new role to this protein, requiring further investigation in the field of myelin formation.

M C Antal

Papers

BBS4 protein has basal body/ciliary localization in sensory organs but extra-ciliary localization in oligodendrocytes during human development