SUMMARY
Netrin1 has been proposed to act from the floor plate (FP) as a long-range diffusible chemoattractant for commissural axons in the embryonic spinal cord. However, netrin1 mRNA and protein are also present in neural progenitors within the ventricular zone (VZ), raising the question of which source of netrin1 promotes ventrally-directed axon growth. Here, we use genetic approaches in mice to selectively remove netrin from different regions of the spinal cord. Our analyses show that the FP is not the source of netrin1 directing axons to the ventral midline while local VZ-supplied netrin1 is required for this step. Furthermore, rather than being present in a gradient, netrin1 protein accumulates on the pial surface adjacent to the path of commissural axon extension. Thus, netrin1 does not act as a long-range secreted chemoattractant for commissural spinal axons, but instead promotes ventrally-directed axon outgrowth by haptotaxis, i.e. directed growth along an adhesive surface.
Multiple studies, involving distinct clinical populations, implicate contactin associated protein-like 2 (CNTNAP2) in aspects of language development and performance. While CNTNAP2 is broadly distributed in developing rodent brain, it shows a striking gradient of frontal cortical enrichment in developing human brain, consistent with a role in patterning circuits that subserve higher cognition and language. To test the hypothesis that CNTNAP2 may be important for learned vocal communication in additional species, we employed in situ hybridization to characterize transcript distribution in the zebra finch, an experimentally tractable songbird for which the neural substrate of this behavior is well established. Consistent with an important role in learned vocalization, Cntnap2 was enriched or diminished in key song control nuclei relative to adjacent brain tissue. Importantly, this punctuated expression was observed in males, but not females, in accord with the sexual dimorphism of neural circuitry and vocal learning in this species. Ongoing functional work will provide important insights into the relationship between Cntnap2 and vocal communication in songbirds and thereby clarify mechanisms at play in disorders of human cognition and language.
In the burying beetles, Nicrophorus orbicollis, it is not clear the extent to which synthesis of Vitellogenin (Vg) is under hormonal control. Juvenile hormone (JH) and ovarian development increase rapidly upon discovery of a carcass, the necessary reproductive resource, but in its absence, treatment with JH does not accelerate ovarian development. Here we investigated the effect of manipulating JH titers on Vg gene expression in the fat bodies of newly eclosed and sexually mature females. Topical applications of the JH analogue methoprene at doses of 200, 300, and 400 microg of methoprene/g beetle to newly eclosed females resulted in up to a 5-fold increase in fat body Vg mRNA levels compared to acetone-treated control females. However, none of these increases were statistically significant. We also measured hemolymph Vg in females subjected to prolonged treatment with an intermediate dose of 300 microg of methoprene/g beetle and found no statistically significant increase in hemolymph Vg following treatment. There was, however, a significantly positive correlation between Vg mRNA and hemolymph Vg. Conversely, although injecting sexually mature females with fluvastatin (an inhibitor of JH biosynthesis in the corpora allata) at a dose of 40 microg/ beetle resulted in significantly decreased JH titers in treated females compared to saline-injected controls, Vg transcription rates were not affected. We suggest that in burying beetles, JH alone is not sufficient to upregulate the expression of the Vg genes and that other factors may be involved in regulating their vitellogenic cycle as well.
Burying beetles Nicrophorus orbicollis exhibit facultative biparental care of young. To reproduce, a male–female burying beetle pair bury and prepare a small vertebrate carcass as food for its altricial young. During a breeding bout, male and female behavior changes synchronously at appropriate times and is coordinated to provide effective care for offspring. Although the ecological and evolutionary factors that shape this remarkable reproductive plasticity are well characterized, the neuromodulation of parental behavior is poorly understood. Juvenile hormone levels rise dramatically at the time beetle parents accept and feed larvae, remain highly elevated during the stages of most active care and fall abruptly when care is terminated. However, hormonal fluctuations alone cannot account for this elaborate control of reproduction. The biogenic amines octopamine (OA), dopamine (DA), and serotonin (5-HT) mediate a diversity of insect reproductive and social behaviors. In this study, we measured whole brain monoamine levels in individual male and female burying beetles and compared OA, DA, and 5-HT profiles between breeding (parental) and nonbreeding, unmated beetles. Remarkably, after 24 h of care, when parental feeding rates begin to peak, DA brain levels increase in breeding beetles when compared to nonbreeding controls. In contrast, brain OA and 5-HT levels did not change significantly. These results provide the first evidence for a potential role of DA in the modulation of burying beetle parental behavior.
The neural and genetic bases of human language development and associated neurodevelopmental disorders, including autism spectrum disorder (ASD), in which language impairment represents a core deficit, are poorly understood. Given that no single animal model can fully capture the behavioral and genetic complexity of ASD, work in songbird, an experimentally tractable animal model of vocal learning, can complement the valuable tool of rodent genetic models and contribute important insights to our understanding of the communication deficits observed in ASD. Like humans, but unlike traditional laboratory animals such as rodents or non-human primates, songbirds exhibit the capacity of vocal learning, a key subcomponent of language. Human speech and birdsong reveal important parallels, highlighting similar developmental critical periods, a homologous cortico-basal ganglia-thalamic circuitry, and a critical role for social influences in the learning of vocalizations. Here I highlight recent advances in using the songbird model to probe the cellular and molecular mechanisms underlying the formation and function of neural circuitry for birdsong and, by analogy, human language, with the ultimate goal of identifying any shared or human unique biological pathways underscoring language development and its disruption in ASD.
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