It is well established that the neurotransmitter serotonin performs essential functions during the course of vertebrate development. The objective of this study was to examine the role of serotonin in the development of two species of frogs that have evolved different developmental modes: direct development and metamorphosis. Directly developing frogs lack the free-swimming, larval stage that is characteristic of most metamorphic frogs and develop directly into the adult phenotype. Metamorphosis is a dramatic change in physiology, behaviour, and life history, which results in an aquatic tadpole transforming into a terrestrial organism. This investigation utilized the metamorphic frog, Xenopus laevis, the African clawed frog, and the directly developing frog, Eleutherodactylus coqui, the coquí frog from Puerto Rico. Developing embryos and tadpoles of E. coqui and X. laevis were treated with several pharmaceutical agents that altered serotonin metabolism including: 5-HT inhibitor, serotonin precursors, 5-HT transporter inhibitor, and 5-HT 1A , 5-HT 2A/C , 5-HT 3 , 5-HT 4 receptor agonists and antagonists. Following treatment, embryos and tadpoles were analyzed using immunocytochemistry and high performance liquid chromatography to determine the effects of the altered serotonergic system on the onset and completion of metamorphosis as well as the progression of direct development. Results indicated that serotonin is important in the modulation of metamorphosis and that disruption of serotonin metabolism resulted in abnormal development of E. coqui. Although differences were noted between the two developmental pathways, it is concluded that serotonin is an essential neurochemical in both metamorphic and directly developing modes.The neurotrophin receptor TrkA plays critical roles in the nervous system by recruiting signaling molecules that activate pathways required for the growth and survival of neurons. Here, we report that APPL1, an adaptor protein implicated in endosomal signaling, is a TrkA-associated protein. APPL1 and TrkA co-immunoprecipitate in sympathetic neurons. We have identified two routes through which this association can occur. APPL1 was isolated as a binding partner for the TrkA-interacting protein GIPC1 from rat brain lysate by mass spectrometry. The PDZ domain of GIPC1 directly engaged the C-terminal sequence of APPL1. This interaction provides a means through which APPL1 may be recruited to TrkA. In addition, the APPL1 PTB domain bound to TrkA, indicating that APPL1 may associate with TrkA independently of GIPC1. Isolation of endosomal fractions by high-resolution centrifugation determined that APPL1, GIPC1 and phospho-TrkA are enriched in the same fractions. Reduction of APPL1 or GIPC1 protein levels suppressed nerve growth factor-dependent ERK and Akt activation and neurite outgrowth in PC12 cells. Together, these results indicate that GIPC1 and APPL1 play a role in TrkA function and suggest that a population of endosomes bearing a complex of APPL1, GIPC1 and activated TrkA may transmit NGF sig...

It is well documented that coordination of feeding behavior in anuran amphibians requires precise coordination of the jaw levators and depressors with the timing of the protraction of the tongue. (for review, see Nishikawa, 2000). However, the neuronal mechanism initiating and synchronizing this coordination is not well understood. In addition to the intermandibularis muscle and tongue musculature in the lower jaw, there is a small, transverse muscle at the tip of the jaw, the m. submentalis. Previous anatomical work has demonstrated the presence of muscle spindles in the submentalis, leading to the hypothesis that the activation of this muscle may provide proprioceptive information to aid in coordinating the feeding biomechanics in Rhinella marina. Here, we demonstrate that the submentalis likely acts as a ‘trigger’ to initiate the hypoglossal nerve to activate the tongue, and without feedback information from the muscle spindles of the submentalis, tongue protraction is compromised.

It is well documented that coordination of feeding behavior in anuran amphibians requires precise coordination of the jaw levators and depressors with the timing of the protraction of the tongue. (for review, see Nishikawa, 2000). However, the neuronal mechanism initiating and synchronizing this coordination is not well understood. In addition to the intermandibularis muscle and tongue musculature in the lower jaw, there is a small, transverse muscle at the tip of the jaw, the m. submentalis. Previous anatomical work has demonstrated the presence of muscle spindles in the submentalis, leading to the hypothesis that the activation of this muscle may provide proprioceptive information to aid in coordinating the feeding biomechanics in Rhinella marina. Here, we demonstrate that the submentalis likely acts as a 'trigger' to initiate the hypoglossal nerve to activate the tongue, and without feedback information from the muscle spindles of the submentalis, tongue protraction is compromised.PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.3131v1 | CC BY 4.0 Open Access | rec:

Our lab is studying the feeding behavior in the marine toad, Bufo marinus, as a model system for the neuronal regulation of coordinated movement. Previous studies have suggested that the brainstem coordinates precise movements through a muscular 'trigger' that signals and initiates pre‐loaded muscle activation. We investigated a small distal muscle in the lower jaw, the submentalis, as the trigger for the feeding behavior in toads. The innervation of this muscle was identified, as well as the distribution of trigeminal nuclei innervating the submentalis. Using high speed videography, we analyzed jaw‐tongue movements before and after denervation of the submentalis. Following denervation, the toads were unable to completely protract their tongues. However, tongue protraction gradually increased and full tongue protraction and successful feeding behavior was observed after 4‐6 attempts, suggesting a potential model for motor learning. Additionally, we have anatomically identified the presence of muscle spindles in the submentalis, suggesting that proprioceptive afferents are regulating the motor output. These data support the idea of the submentalis muscle acting as a trigger for timed feeding movements and the importance of the submentalis in coordinating jaw‐tongue movement.