Arantza Barrios

Eph/Ephrin signaling regulates the mesenchymal-to-epithelial transition of the paraxial mesoderm during somite morphogenesis.

BACKGROUND During somitogenesis, segmental patterns of gene activity provide the instructions by which mesenchymal cells epithelialize and form somites. Various members of the Eph family of transmembrane receptor tyrosine kinases and their Ephrin ligands are expressed in a segmental pattern in the rostral presomitic mesoderm. This pattern establishes a receptor/ligand interface at each site of somite furrow formation. In the fused somites (fss/tbx24) mutant, lack of intersomitic boundaries and epithelial somites is accompanied by a lack of Eph receptor/Ephrin signaling interfaces. These observations suggest a role for Eph/Ephrin signaling in the regulation of somite epithelialization. RESULTS We show that restoration of Eph/Ephrin signaling in the paraxial mesoderm of fss mutants rescues most aspects of somite morphogenesis. First, restoration of bidirectional or unidirectional EphA4/Ephrin signaling results in the formation and maintenance of morphologically distinct boundaries. Second, activation of EphA4 leads to the cell-autonomous acquisition of a columnar morphology and apical redistribution of beta-catenin, aspects of epithelialization characteristic of cells at somite boundaries. Third, activation of EphA4 leads to nonautonomous acquisition of columnar morphology and polarized relocalization of the centrosome and nucleus in cells on the opposite side of the forming boundary. These nonautonomous aspects of epithelialization may involve interplay of EphA4 with other intercellular signaling molecules. CONCLUSIONS Our results demonstrate that Eph/Ephrin signaling is an important component of the molecular mechanisms driving somite morphogenesis. We propose a new role for Eph receptors and Ephrins as intercellular signaling molecules that establish cell polarity during mesenchymal-to-epithelial transition of the paraxial mesoderm.

PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans

Appetitive behaviors require complex decision making that involves the integration of environmental stimuli and physiological needs. C. elegans mate searching is a male-specific exploratory behavior regulated by two competing needs: food and reproductive appetite. We found that the pigment dispersing factor receptor (PDFR-1) modulates the circuit that encodes the male reproductive drive that promotes male exploration following mate deprivation. PDFR-1 and its ligand, PDF-1, stimulated mate searching in the male, but not in the hermaphrodite. pdf-1 was required in the gender-shared interneuron AIM, and the receptor acted in internal and external environment-sensing neurons of the shared nervous system (URY, PQR and PHA) to produce mate-searching behavior. Thus, the pdf-1 and pdfr-1 pathway functions in non–sex-specific neurons to produce a male-specific, goal-oriented exploratory behavior. Our results indicate that secretin neuropeptidergic signaling is involved in regulating motivational internal states.

Glia-derived neurons are required for sex-specific learning in C. elegans

Sex differences in behaviour extend to cognitive-like processes such as learning, but the underlying dimorphisms in neural circuit development and organization that generate these behavioural differences are largely unknown. Here we define at the single-cell level—from development, through neural circuit connectivity, to function—the neural basis of a sex-specific learning in the nematode Caenorhabditis elegans. We show that sexual conditioning, a form of associative learning, requires a pair of male-specific interneurons whose progenitors are fully differentiated glia. These neurons are generated during sexual maturation and incorporated into pre-exisiting sex-shared circuits to couple chemotactic responses to reproductive priorities. Our findings reveal a general role for glia as neural progenitors across metazoan taxa and demonstrate that the addition of sex-specific neuron types to brain circuits during sexual maturation is an important mechanism for the generation of sexually dimorphic plasticity in learning.

Exploratory decisions of the Caenorhabditis elegans male: A conflict of two drives

The ability to generate behavioral plasticity according to ever-changing physiological demands and environmental conditions is a universal feature of decision-making circuits in all animals. Decision-making requires complex integration of internal states with sensory context. As a mate searching strategy, the Caenorhabditis elegans male modifies his exploratory behavior in relation to a source of food according to recent sensory experience with mates. Information about the reproductive and nutritional status of the male is also incorporated in his choice of exploratory behavior. The study of mate searching in the C. elegans male, a genetic model organism with a nervous system of only 383 neurons, provides the opportunity to elucidate the molecular and cellular mechanisms of state-dependent control of behavior and sensory integration. Here I review our progress in understanding the physiological and environmental regulation of the males exploratory choices - to explore in search of mates or to exploit a source of food - and the neural circuits and neuromodulator pathways underlying this decision.

A direct glia-to-neuron natural transdifferentiation ensures nimble sensory-motor coordination of male mating behaviour

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism to generate male-specific neurons in Caenorhabditis elegans, through the direct transdifferentiation of sex-shared glial cells. This glia-to-neuron cell fate switch occurs during male sexual maturation under the cell-autonomous control of the sex-determination pathway. We show that the neurons generated are cholinergic, peptidergic and ciliated putative proprioceptors which integrate into male-specific circuits for copulation. These neurons ensure coordinated backward movement along the mate’s body during mating. One step of the mating sequence regulated by these neurons is an alternative readjustment movement performed when intromission becomes difficult to achieve. Our findings reveal programmed transdifferentiation as a developmental mechanism underlying flexibility in innate behaviour.

Glia developmental plasticity couples behaviour to reproductive needs

Introduction: Parapineal (PpO) neurons develop asymmetric connectivity to the left habenula (lHb) in the dorsal diencephalon of embryonic and larval zebrafish. Recent studies relate this asymmetric connectivity with sensory responses to light. However, the structural and functional bases of this behaviour are still unknown. To begin addressing this issue we investigated the axonal structural configuration and distribution of pre-synaptic proteins in PpO-lHb projections of zebrafish larvae searching for plastic changes modulated by light. Material and Methods: PpO-lHb connectivity was visualised by confocal microscopy in dissected brains of Tg(foxd3:GFP) zebrafish larvae maintained under different Light (L) and Dark (D) conditions: (a) cycles of 14L and 10D hours [L:D], (b) continuous dark [D:D], and (c) continuous light [L:L]. After fixation, anti-GFP and anti-SNAP-25 inmunofluorescence were performed in peeled brains and confocal images acquired. 3D image analysis included manual/automatic segmentation, computing shape descriptors of PpO projections, and pre-synaptic puncta quantification. Results: PpO projections show a characteristic morphology that undergo rhythmic changes in larvae subject to L:D cycles, particularly during the L-D and D-L transitions. Also, the number and composition of pre-synaptic protein expression in the PpO-lHb circuit show rhythmic remodelling two hours before the L-D and D-L transitions. This features were not found in the D:D and L:L conditions. Discussion: These results suggest that the PpO-lHb circuit in zebrafish larvae responds to Light:Dark rhythmical changes through a mechanismof plasticity, generating structural and synaptic remodelling of PpO projections. Funding: ICMP09-015-F, FONDECYT (3160421, 1161274, 1151029), CONICYT PIA ACT1402, FONDAP 15150012.