From axon–glial signalling to myelination: the integrating role of oligodendroglial Fyn kinase

Central nervous system myelination requires recognition and signalling processes between neuronal axons and oligodendrocytes. Complex cellular rearrangements occur in myelination-competent oligodendrocytes requiring spatio-temporal control mechanisms. Although the molecular repertoire is becoming increasingly transparent, the signalling mechanisms governing myelination initiation are only poorly understood. The non-receptor tyrosine kinase Fyn has been implicated in axon–glial signal transduction and in several cellular processes required for oligodendrocyte maturation and myelination. Here, we review oligodendroglial Fyn signalling and discuss the role of Fyn in axon–glia interaction mediating myelination.     

The first mite: insect genealogy in Hooke’s Micrographia*

What happens when you take the idea of the biblical Adam—the first human – and apply it to insects? You create an origin story for Nature’s tiniest creatures, one that gives them ‘a Pedigree as ancient as the first creation’. This the naturalist Robert Hooke argued in his treatise, the Micrographia (1665). In what follows, I will retrace how Hooke endeavoured to show that insects—then widely believed to have arisen out of the dirt – were the products of an ancient lineage. These genealogies, while constructed from empirical observation, were conjectures of the imagination. Section 2 shows how Hooke introduced the concept of a ‘prime parent’ (an Adam-insect) to explain the anatomical similarities between ‘mites’. Section 3 demonstrates how Hooke defined the family of “gnats” as tiny machines built from the same components and relates Hookean genealogies to contemporary ideas about Noah’s Ark. Section 4 shows how Hooke outlined the morphology of ‘insects’ (delineating what we now call arthropods). Section 5 explores how Hooke used fossils to study these animals in the distant past. In sum, Hooke was turning natural history – collecting and describing insects – into natural history: reconstructing their origins.     

A strain of amaril virus isolated from Aedes africanus in the Ivory Coast]

The yellow fever virus has been isolated from a pool of Aedes africanus caught on men in a region situated between forest and savannah near Touba, in the Ivory Coast. This isolation, occurring at an interepidemic period, proves for the first time in West Africa, the part played by this mosquito in the transmission of the yellow fever virus.     

Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer

The mammalian Y chromosome acts as a dominant male determinant as a result of the action of a single gene, Sry, whose role in sex determination is to initiate testis rather than ovary development from early bipotential gonads. It does so by triggering the differentiation of Sertoli cells from supporting cell precursors, which would otherwise give follicle cells. The related autosomal gene Sox9 is also known from loss-of-function mutations in mice and humans to be essential for Sertoli cell differentiation; moreover, its abnormal expression in an XX gonad can lead to male development in the absence of Sry. These genetic data, together with the finding that Sox9 is upregulated in Sertoli cell precursors just after SRY expression begins, has led to the proposal that Sox9 could be directly regulated by SRY. However, the mechanism by which SRY action might affect Sox9 expression was not understood. Here we show that SRY binds to multiple elements within a Sox9 gonad-specific enhancer in mice, and that it does so along with steroidogenic factor 1 (SF1, encoded by the gene Nr5a1 (Sf1)), an orphan nuclear receptor. Mutation, co-transfection and sex-reversal studies all point to a feedforward, self-reinforcing pathway in which SF1 and SRY cooperatively upregulate Sox9 and then, together with SF1, SOX9 also binds to the enhancer to help maintain its own expression after that of SRY has ceased. Our results open up the field, permitting further characterization of the molecular mechanisms regulating sex determination and how they have evolved, as well as how they fail in cases of sex reversal.     

Type IV collagens regulate BMP signalling in Drosophila

Dorsal-ventral patterning in vertebrate and invertebrate embryos is mediated by a conserved system of secreted proteins that establishes a bone morphogenetic protein (BMP) gradient. Although the Drosophila embryonic Decapentaplegic (Dpp) gradient has served as a model to understand how morphogen gradients are established, no role for the extracellular matrix has been previously described. Here we show that type IV collagen extracellular matrix proteins bind Dpp and regulate its signalling in both the Drosophila embryo and ovary. We provide evidence that the interaction between Dpp and type IV collagen augments Dpp signalling in the embryo by promoting gradient formation, yet it restricts the signalling range in the ovary through sequestration of the Dpp ligand. Together, these results identify a critical function of type IV collagens in modulating Dpp in the extracellular space during Drosophila development. On the basis of our findings that human type IV collagen binds BMP4, we predict that this role of type IV collagens will be conserved.     

An Asian perspective on early human dispersal from Africa

The past decade has seen the Pliocene and Pleistocene fossil hominin record enriched by the addition of at least ten new taxa, including the Early Pleistocene, small-brained hominins from Dmanisi, Georgia, and the diminutive Late Pleistocene Homo floresiensis from Flores, Indonesia. At the same time, Asia's earliest hominin presence has been extended up to 1.8 Myr ago, hundreds of thousands of years earlier than previously envisaged. Nevertheless, the preferred explanation for the first appearance of hominins outside Africa has remained virtually unchanged. We show here that it is time to develop alternatives to one of palaeoanthropology's most basic paradigms: 'Out of Africa 1'.