Biomedical subjects

Michael R Akins

Publications and source records attributed to Michael R Akins.

3 recordsLinked to original sources

PubMed2006

Axon behavior in the olfactory nerve reflects the involvement of catenin-cadherin mediated adhesion.

The projection of olfactory sensory neuron (OSN) axons to the olfactory bulb (OB) is a complex but well-regulated process. Although odorant receptor proteins, and other molecules, are implicated in this process, our understanding remains incomplete. We demonstrate that axons remain restricted to the outer olfactory nerve layer (ONLo) until they are proximal to their target glomeruli, where they enter the inner ONL (ONLi), dividing the ONL into extension and sorting zones. Sorting is likely contingent on cell:cell interactions mediated in part by cell adhesion molecules. The cadherins are a large family of adhesion molecules whose function is contingent on their intracellular binding partners, the catenins, which in turn link to the cytoskeleton. We previously demonstrated that the organization of the cytoskeleton changed as olfactory sensory neuron axons moved from the ONLo to the ONLi. To further assess the role of cadherin mediated adhesion in the developing mouse ONL, we localized alpha-, beta-, gamma-, delta-, and p120-catenins as well as neural cadherin (N-cadherin; CDH2) in the OB. alpha- and beta-catenins are found throughout the OB and are uniform throughout the ONL. In contrast, gamma-catenin and CDH2 are expressed predominantly in the ONLo during perinatal development, but are uniform across the ONL beginning at P7 and into adulthood. Finally, p120- and delta-catenins are expressed in nonoverlapping patterns by olfactory axons and OB neuronal dendrites, respectively. We conclude that gamma-catenin-mediated CDH2 adhesion may influence OSN targeting by restricting axons to the ONLo until they reach the appropriate domain of the OB.

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PubMed2006

Cell-cell interactions in synaptogenesis.

Synaptogenesis is a finely organized process, intriguing in its precise temporal and spatial resolution. It occurs as the dendrite of a postsynaptic neuron and an incoming axon communicate at defined sites to establish a stable synapse together. The molecular cues that guide synaptogenesis are now beginning to be identified, and cell surface interactions at synaptic sites participate prominently in the key steps. Interactions include trans-synaptic adhesion of pre- and post-synaptic neurons but also binding to non-neuronal neighboring cells and the extracellular matrix. These signals recruit scaffolding molecules, other adhesion molecules, and neurotransmitter receptors to bring together the key components of functional synapses. Recent progress provides stimulating insights into the role of adhesion and signaling molecules in the formation and function of synaptic specializations.

Animals↗

PubMed2006

Cytoskeletal organization of the developing mouse olfactory nerve layer.

Olfactory sensory neuron (OSN) axonal extension and targeting occur within the olfactory nerve layer (ONL) of the olfactory bulb (OB). The ONL can be differentiated into sublaminae: the outer (ONLo), where axons broadly target regions of the OB in tight fascicles, and inner (ONLi), where axons perform final targeting in loosely organized fascicles. During perinatal development, cadherin-2 and its binding partner, gamma-catenin, are preferentially expressed by OSN axons in the ONLo vs. the ONLi. Given the expression of these cytoskeleton-associated molecules, we hypothesized that cytoskeletal elements of OSN axons may be differentially expressed across the ONL. We therefore examined cytoskeletal organization of OSN axons in the ONL, focusing on the day of birth (P0). We show that microfilaments, microtubules, and the intermediate filament (IF) vimentin are homogeneously expressed across the ONL at P0. In contrast, the IFs peripherin and alpha-internexin are preferentially localized to the ONLo at P0, with alpha-internexin expressed by a restricted subset of OSNs. We also show that OSN axons in the ONLo are significantly smaller than those in the ONLi. The data demonstrate that, as OSN axons begin to exit the ONLo and target a specific region of the OB, there is a down-regulation of cytoskeletal elements and bound extracellular adhesion molecules. The increase in axon diameter may reflect additional mechanisms involved in glomerular targeting or the formation of the large terminal boutons of OSN axons within glomeruli.

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