A sex-specific switch in a single glial cell patterns the apical extracellular matrix.

Apical extracellular matrix (aECM) constitutes the interface between every tissue and the outside world. It is patterned into diverse tissue-specific structures through unknown mechanisms. Here, we show that a male-specific genetic switch in a single C. elegans glial cell patterns the overlying aECM from a solid sheet to an ∼200 nm pore, thus allowing a male sensory neuron to access the environment. Using cell-specific genetic sex reversal, we find that this switch reflects an inherent sex difference in the glial cell that is independent of the sex identity of the surrounding neurons. Through candidate and unbiased genetic screens, we find that this glial sex difference is controlled by factors shared with neurons (mab-3, lep-2, and lep-5) as well as previously unidentified regulators whose effects may be glia specific (nfya-1, bed-3, and jmjd-3.1). The switch results in male-specific glial expression of a secreted Hedgehog-related protein, GRL-18, that we discover localizes to transient nanoscale rings at sites where aECM pores will form. Using electron microscopy, we find that blocking male-specific gene expression in glia prevents pore formation, whereas forcing male-specific glial gene expression induces an ectopic pore. Thus, a switch in gene expression in a single cell is necessary and sufficient to pattern aECM into a specific structure. Our results highlight that aECM is not a simple homogeneous meshwork, but instead is composed of discrete local features that reflect the identity of the underlying cells.

Reimagining journal clubs for inclusive scientific training.

'Canonical' journal clubs, which rely on a presenter guiding a group through the figures of a scientific article, do not fully realize their training potential. We provide a blueprint and resources for effectively leveraging journal clubs to meet specific training objectives and to further equity, diversity, inclusion, and belonging goals.

A sex-specific switch in a single glial cell patterns the apical extracellular matrix.

Apical extracellular matrix (aECM) constitutes the interface between every tissue and the outside world. It is patterned into diverse tissue-specific structures through unknown mechanisms. Here, we show that a male-specific genetic switch in a single C. elegans glial cell patterns the aECM into a ∻200 nm pore, allowing a male sensory neuron to access the environment. We find that this glial sex difference is controlled by factors shared with neurons ( mab-3, lep-2, lep-5 ) as well as previously unidentified regulators whose effects may be glia-specific ( nfya-1, bed-3, jmjd-3.1 ). The switch results in male-specific expression of a Hedgehog-related protein, GRL-18, that we discover localizes to transient nanoscale rings at sites of aECM pore formation. Blocking male-specific gene expression in glia prevents pore formation, whereas forcing male-specific expression induces an ectopic pore. Thus, a switch in gene expression in a single cell is necessary and sufficient to pattern aECM into a specific structure.

Teaching About Sex and Gender in Neuroscience: More Than Meets the "XY".

Offering courses on the neuroscience of sex and gender can help support an inclusive curriculum in neuroscience. At the same time, developing and teaching such courses can be daunting to even the most enthusiastic educators, given the subject's complexities, nuances, and the difficult conversations that it invites. The authors of this article have all developed and taught such courses from different perspectives. Our aim is to provide educators with an overview of important conceptual topics as well as a comprehensive, but non-exhaustive, guide to resources for teaching about sex/gender in neuroscience based on our collective experience teaching courses on the topic. After defining vital terminology and briefly reviewing the biology of sex and sex determination, we describe some common topics within the field and contrast our current nuanced understandings from outdated misconceptions in the field. We review how (mis)representation of the neuroscience of sex/gender serves as a case study for how scientific results are communicated and disseminated. We consider how contextualization of sex/gender neuroscience research within a broader historical and societal framework can give students a wider perspective on the enterprise of science. Finally, we conclude with a brief discussion on how to choose learning goals for your course and implementation notes.

Genetic control of the segregation of pain-related sensory neurons innervating the cutaneous versus deep tissues.

Mammalian pain-related sensory neurons are derived from TrkA lineage neurons located in the dorsal root ganglion. These neurons project to peripheral targets throughout the body, which can be divided into superficial and deep tissues. Here, we find that the transcription factor Runx1 is required for the development of many epidermis-projecting TrkA lineage neurons. Accordingly, knockout of Runx1 leads to the selective loss of sensory innervation to the epidermis, whereas deep tissue innervation and two types of deep tissue pain are unaffected. Within these cutaneous neurons, Runx1 suppresses a large molecular program normally associated with sensory neurons that innervate deep tissues, such as muscle and visceral organs. Ectopic expression of Runx1 in these deep sensory neurons causes a loss of this molecular program and marked deficits in deep tissue pain. Thus, this study provides insight into a genetic program controlling the segregation of cutaneous versus deep tissue pain pathways.

Molecular organization of vomeronasal chemoreception.

The vomeronasal organ (VNO) has a key role in mediating the social and defensive responses of many terrestrial vertebrates to species- and sex-specific chemosignals. More than 250 putative pheromone receptors have been identified in the mouse VNO, but the nature of the signals detected by individual VNO receptors has not yet been elucidated. To gain insight into the molecular logic of VNO detection leading to mating, aggression or defensive responses, we sought to uncover the response profiles of individual vomeronasal receptors to a wide range of animal cues. Here we describe the repertoire of behaviourally and physiologically relevant stimuli detected by a large number of individual vomeronasal receptors in mice, and define a global map of vomeronasal signal detection. We demonstrate that the two classes (V1R and V2R) of vomeronasal receptors use fundamentally different strategies to encode chemosensory information, and that distinct receptor subfamilies have evolved towards the specific recognition of certain animal groups or chemical structures. The association of large subsets of vomeronasal receptors with cognate, ethologically and physiologically relevant stimuli establishes the molecular foundation of vomeronasal information coding, and opens new avenues for further investigating the neural mechanisms underlying behaviour specificity.