Commissureless acts as a substrate adapter in a conserved Nedd4 E3 ubiquitin ligase pathway to promote axon growth across the midline.

In both vertebrates and invertebrates, commissural neurons prevent premature responsiveness to the midline repellant Slit by downregulating surface levels of its receptor Roundabout1 (Robo1). In , Commissureless (Comm) plays a critical role in this process; however, there is conflicting data on the underlying molecular mechanism. Here, we demonstrate that the conserved PY motifs in the cytoplasmic domain of Comm are required allow the ubiquitination and lysosomal degradation of Robo1.

Intracellular Trafficking Mechanisms that Regulate Repulsive Axon Guidance.

Friedrich Bonhoeffer made seminal contributions to the study of axon guidance in the developing nervous system. His discoveries of key cellular and molecular mechanisms that dictate wiring specificity laid the foundation for countless investigators who have followed in his footsteps. Perhaps his most significant contribution was the cloning and characterization of members of the conserved ephrin family of repulsive axon guidance cues.

Inverse Drug Screening of Bioelectric Signaling and Neurotransmitter Roles: Illustrated Using a Tail Regeneration Assay.

embryos and larvae are an ideal model system in which to study the interplay between genetics, physiology, and anatomy in the control of structure and function. An important emerging field is the study of bioelectric signaling, the exchange of ion- and neurotransmitter-mediated messages among all types of cells (not just nerve and muscle cells), in the regulation of growth and form during embryogenesis, regeneration, and cancer. To facilitate the mechanistic investigation of bioelectric events in vivo, it is necessary to identify the endogenous signaling machinery involved in any patterning process of interest.

Physiological inputs regulate species-specific anatomy during embryogenesis and regeneration.

A key problem in evolutionary developmental biology is identifying the sources of instructive information that determine species-specific anatomical pattern. Understanding the inputs to large-scale morphology is also crucial for efforts to manipulate pattern formation in regenerative medicine and synthetic bioengineering. Recent studies have revealed a physiological system of communication among cells that regulates pattern during embryogenesis and regeneration in vertebrate and invertebrate models.

Neurotransmitter signaling pathways required for normal development in Xenopus laevis embryos: a pharmacological survey screen.

Neurotransmitters are not only involved in brain function but are also important signaling molecules for many diverse cell types. Neurotransmitters are widely conserved, from evolutionarily ancient organisms lacking nervous systems through man. Here, results are reported from a loss- and gain-of-function survey, using pharmacological modulators of several neurotransmitter pathways to examine possible roles for these pathways in normal embryogenesis.