Office: (317)-278-9621
Lab:  (317)-278-9623/9622

E-Mail:  ehashino@iupui.edu
 

Our laboratory studies the molecular mechanisms underlying neuronal identity and specification. The model systems we are currently using are inner ear sensory neurons, cranial parasympathetic neurons and bone marrow stromal cells. We utilize a combination of cell biology, molecular biology and imaging techniques to delineate the mechanisms by which soluble proteins and transcription factors positively or negatively regulate cell cycle progression, gene expression, and cell morphology, thereby promoting neuronal induction and differentiation. Our goal is to establish a means to generate lineage-specific neurons from adult bone marrow-derived stem cells.

During early development, cells lining on the rostro-ventral region of the otocyst (presumptive inner ear) acquire their identity as neural progenitors and migrate out of the otocyst to form the VIII ganglion. Little is known about the molecular mechanisms involved in the induction, migration and differentiation of VIII ganglion neurons (inner ear sensory neurons). Using various mutant mice and primary culture system, we are trying to identify molecular factors that promote neurogenesis or neuronal differentiation from undifferentiated cells in the otocyst.

We have recently identified glial cell line-derived neurotrophic factor (GDNF) as a target-derived factors for parasympathetic ciliary ganglion neurons. Our results indicate that GDNF is synthesized in target eye tissues of ciliary ganglion neurons during early embryogenesis, suggesting a role of this protein in neuronal differentiation processes. We are currently testing whether GDNF plays a role in (1) neurogenesis, (2) axon guidance or (3) neurotransmitter receptor expression, in developing ciliary ganglion neurons.<

We have obtained evidence that adult bone marrow stromals cells express neural stem cell markers and that they differentiate into post-mitotic neural progenitors in response to neural induction signals. We are testing if these marrow-derived neural stem cells are able to differentiate into lineage-specific neurons, and if so, what types of extrinsic signals are required for the marrow-derived stem cells to become competent to commit to a specific neuronal lineage.

Publications:

Hashino, E., Dolnick, R.Y. and Cohan, C.S. Developing vestibular ganglion neurons switch trophic sensitivity from BDNF to GDNF after target innervation. J. Neurobiol. 38: 414-427, 1999.

Hashino, E., Johnson, E.M. Jr., Milbrandt, J., Shero, M., Salvi, R.J. and Cohan, C.S. Multiple actions of neurturin correlate with spatiotemporal patterns of Ret expression in developing chick cranial ganglion neurons. J. Neurosci. 19: 8476-8486, 1999.

Hashino, E., Shero, M. and Salvi, R.J. Lysosomal augmentation during aminoglycoside uptake in cochlear hair cells. Brain Res. 887: 90-97, 2000.

Sun, H., Hashino, E., Ding, D.L. and Salvi, R.J. Reversible and irreversible damage to cochlear afferent neurons by kainic acid excitotoxicity. J. Comp. Neurol. 430: 172-181, 2001.

Hashino, E., Shero, M., Junghans, D., Rohrer, H., Milbrandt, J. and Johnson, E.M. Jr. GDNF and neurturin are target-derived factors essential for cranial parasympathetic neuron development. Development 128: 3773-3782, 2001.

Romand, R., Hashino, E., Dolle, P., Chambon, P. and Ghyselinck, N.B. The retinoic acid receptors RARa and RARg are required for inner ear development. Mech. Dev. 119: 213-223, 2002.

Romand, R., Niederreither, K., Abu-Abed, S., Petkovich, M., Fraulob, V., Hashino, E. and Dolle, P. Complementary expression patterns of retinoic acid synthesizing and –metabolizing enzymes in prenatal mouse inner ear structures. Mech. Dev. (in press).


Return to Faculty List
Return Home