The Fragile X Messenger Ribonucleoprotein 1 Participates in Axon Guidance Mediated by the Wnt/Planar Cell Polarity Pathway.

The Planar cell polarity (PCP) pathway is known to mediate the function of the Wnt proteins in growth cone guidance. Here, we show that the PCP pathway may directly influence local protein synthesis within the growth cones. We found that Fragile X Messenger Ribonucleoprotein 1 (FMRP) interacts with Fzd3.

Biochemical and Cellular Assays to Study Mechanisms of PCP Signaling in Axon Guidance.

Understanding biochemical and cellular mechanisms of how PCP components regulate axon guidance is important for understanding brain development and may lead to new therapeutic approaches for neural repair. Meanwhile, axonal growth cones are a highly polarized structure and are a great experimental system. Therefore, some of these novel mechanisms we are uncovering for axon guidance may be applicable for PCP signaling in general.

In Vitro Explant Assays and Cultures to Study PCP Signaling in Axon Guidance.

In vitro studies have provided valuable insights to the function and mechanisms in axon guidance. In this chapter, we will introduce the rodent "open-book" assay, pre- or postcrossing explant culture and the dissociated neuron culture. They have been used to discover mechanism which we have gone on to validate or will confirm using in vivo genetic approaches.

Characterization of Axon Guidance Phenotypes in Wnt/PCP Mutant Mice.

Our lab showed that the Wnt family proteins can function as axon guidance molecules and the planar cell polarity (PCP) pathway mediates the function of Wnts in axon guidance. One of the key evidences was by identifying the axon guidance defects in knockout or conditional knockout animals. We utilized a variety of axon tracing and labeling techniques, including immunohistochemistry (IHC), DiI, BDA, and fluorescent reporters (GFP or tdTomato).

FLRT2 and FLRT3 Cooperate in Maintaining the Tangential Migratory Streams of Cortical Interneurons during Development.

Neuron migration is a hallmark of nervous system development that allows gathering of neurons from different origins for assembling of functional neuronal circuits. Cortical inhibitory interneurons arise in the ventral telencephalon and migrate tangentially forming three transient migratory streams in the cortex before reaching the final laminar destination. Although migration defects lead to the disruption of inhibitory circuits and are linked to aspects of psychiatric disorders such as autism and schizophrenia, the molecular mechanisms controlling cortical interneuron development and final layer positioning are incompletely understood.

Genetic ablation of the Rho GTPase Rnd3 triggers developmental defects in internal capsule and the globus pallidus formation.

The forebrain includes the cerebral cortex, the thalamus, and the striatum and globus pallidus (GP) in the subpallium. The formation of these structures and their interconnections by specific axonal tracts take place in a precise and orchestrated time and spatial-dependent manner during development. However, the knowledge of the molecular and cellular mechanisms that are involved is rather limited.