Loss of CRMP1 and CRMP2 results in migration defects of Purkinje cells in the X lobule of the mouse cerebellum.

The three-layered structure of the mammalian cerebellar cortex is generated through the coordinated migration of cerebellar neurons. Purkinje cells migrate and form a three- to four-cell-thick aggregate below the external granule cell layer during the embryonic stage, and align to form a monocellular arrangement in the Purkinje cell layer during the postnatal period. We previously reported the involvement of Cdk5-mediated CRMP2 phosphorylation in Purkinje cell migration and the synergistic roles of two other CRMPs, CRMP1 and CRMP4.

Regulation of axon pruning of mossy fiber projection in hippocampus by CRMP2 and CRMP4.

Axon pruning facilitates the removal of ectopic and misguided axons and plays an important role in neural circuit formation during brain development. Sema3F and its receptor neuropilin-2 (Nrp2) have been shown to be involved in the stereotyped pruning of the infrapyramidal bundle (IPB) of mossy fibers of the dentate gyrus (DG) in the developing hippocampus. Collapsin response mediator proteins (CRMPs) were originally identified as an intracellular mediator of semaphorin signaling, and the defective pruning of IPB was recently reported in CRMP2-/- and CRMP3-/- mice.

Requirement of CRMP2 Phosphorylation in Neuronal Migration of Developing Mouse Cerebral Cortex and Hippocampus and Redundant Roles of CRMP1 and CRMP4.

The mammalian cerebral cortex is characterized by a 6-layer structure, and proper neuronal migration is critical for its formation. Cyclin-dependent kinase 5 (Cdk5) has been shown to be a critical kinase for neuronal migration. Several Cdk5 substrates have been suggested to be involved in ordered neuronal migration.

Phosphorylation of CRMP2 is required for migration and positioning of Purkinje cells: Redundant roles of CRMP1 and CRMP4.

Proper migration and positioning of Purkinje cells are important for formation of the developing cerebellum. Although several cyclin-dependent kinase 5 (Cdk5) substrates are known to be critical for ordered neuronal migration, there are no reports of mutant mouse-based, in vivo studies on the function of Cdk5-phosphorylation substrates in migration of Purkinje cells. We focused on the analysis of collapsin response mediator protein 2 (CRMP2), one of the Cdk5 substrates, because a previous study reported migration defects of cortical neurons with shRNA-mediated knockdown of CRMP2.

Opposing Morphogenetic Defects on Dendrites and Mossy Fibers of Dentate Granular Neurons in CRMP3-Deficient Mice.

Collapsin response mediator proteins (CRMPs) are highly expressed in the brain during early postnatal development and continue to be present in specific regions into adulthood, especially in areas with extensive neuronal plasticity including the hippocampus. They are found in the axons and dendrites of neurons wherein they contribute to specific signaling mechanisms involved in the regulation of axonal and dendritic development/maintenance. We previously identified CRMP3's role on the morphology of hippocampal CA1 pyramidal dendrites and hippocampus-dependent functions.

Phosphorylation of CRMP2 (collapsin response mediator protein 2) is involved in proper dendritic field organization.

Collapsin response mediator proteins (CRMPs) are intracellular proteins that mediate signals for several extracellular molecules, such as Semaphorin3A and neurotrophins. The phosphorylation of CRMP1 and CRMP2 by Cdk5 at Ser522 is involved in axonal guidance and spine development. Here, we found that the Ser522-phosphorylated CRMP1 and/or CRMP2 are enriched in the dendrites of cultured cortical neurons and P7 cortical section.

Collaborative engineering: 3-D optical imaging and gas exchange simulation of in-vitro alveolar constructs.

This paper reports on the computational simulation and modeling of an in vitro alveolar construct system along the optical coherence microscopy (OCM) methods for visualizing engineered tissue. The optical imaging methods will be compared to immunohistochemical light microscopy samples of engineered alveolar constructs. Results show depth images of the alveolar tissue construct for a bilayer construct, as well as predictions of the gas exchange process in a simple model of a bio-reactor hosting the construct.

Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease.

Collapsin response mediating protein-2 (CRMP2) has been identified as an intracellular protein mediating Semaphorin3A (Sema3A), a repulsive guidance molecule. In this study, we demonstrate that cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3beta (GSK3beta) plays a critical role in Sema3A signalling. In In vitro kinase assay, Cdk5 phosphorylated CRMP2 at Ser522, while GSK3beta did not induce any phosphorylation of CRMP2.