Section: Research

Postdoctoral Position Available

Gerald Schwarting, Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Cell Biology

Other Affiliation(s):
   Program in Neuroscience
   Shriver Center

Axon Guidance in the Developing Olfactory System

In collaboration with Jim Crandall, we are investigating guidance of connections between sensory neurons in the olfactory epithelium and their targets on the rostral telencephalon. Recent evidence demonstrates that permissive and non-permissive axon guidance cues are differentially expressed by subsets of ensheathing cells at the earliest stages of olfactory development. For example, one member of the semaphorin family, Sema3A is expressed by ensheathing cells in the ventral olfactory bulb (OB) and divides the entire OB into two separate but equal targets, one lateral and one medial. Axons that express neuropilin-1 (Npn-1) are repelled by Sema3A. Thus, Npn-1⁺ axons in the lateral olfactory epithelium (OE) are guided to the lateral OB and Npn-1⁺ axons in the medial OE are guided to the medial OB. As the OB grows between E11 and E13 in the mouse, the pattern of Sema3A changes along the rostrocaudal axis (Fig. 1). As a result, Sema3A subdivides the OB into four compartments along medial/lateral and rostral/caudal axes. One consequence of this expression pattern is that axons expressing a given odorant receptor converge onto one rostrolateral glomerulus and to one ventromedial glomerulus. This pattern is determined by coordinated Sema3A and Npn-1 expression rather than by the odorant receptors themselves. We have also identified a fifth compartment at the ventral midline of the OB, where Npn-1 axons are excluded. Axons expressing lactosamine-containing glycans (LCG) preferentially grow through an extracellular matrix enriched in laminin-8, galectin-1 (and Sema3A) to targets in the ventral OB and are complementary to Npn-1 axon trajectories. These studies suggest that axon guidance is governed by restricted expression of permissive and non-permissive cues that successively restrict subsets of axons into more refined target regions of the developing OB. Our objective is to identify additional guidance cues that further subdivide these targeting compartments into smaller and smaller segments of the OB until precise convergence of axons onto a small number of glomeruli is achieved.

Cell Migration in the Developing Olfactory System

In collaboration with Stu Tobet, we are investigating factors that regulate the migration of luteinizing hormone-releasing hormone (LHRH) neurons. In embryonic mice about 2500 neurons migrate from the vomeronasal organ (VNO) in the nose across the cribriform plate to the forebrain. Approximately half of these migrating neurons contain LHRH and their migration to the ventral forebrain is essential for reproductive competence in mature animals. We have previously shown that LHRH neurons use TAG-1⁺ axons as guides. We have also shown that cell migration can be modulated in vivo and in vitro by altering the expression of adhesion molecules, such as PSA-NCAM, that are expressed on axons and migrating cells. In addition, GABA, which is known to affect migration in other systems, is expressed by LHRH neurons and influences their rate of migration. We have recently shown that the netrin-1 receptor, deleted in colon cancer (DCC) is expressed by many TAG-1⁺ cells in the VNO that extend axons into the ventral forebrain. In DCC mutant mice, these axons fail to turn ventrally once they reach the forebrain (Fig. 2). As a result, most LHRH neurons follow these misguided axons into the medial wall of the cortex rather than to the hypothalamus. Fewer than 10% of the normal number of LHRH neurons migrate to the ventral forebrain in DCC-/- mice compared to wild-type littermates.

Ongoing Projects

Office: Shriver
Phone: (781) 642-0138/0148
E-mail: Gerald.Schwarting@umassmed.edu
Keywords: Neurobiology, Cell Biology, Developmental Biology

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Schwarting for additional details.