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The Journal of Neuroscience, February 28, 2007, 27(9):2290-2297; doi:10.1523/JNEUROSCI.5571-06.2007

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Development/Plasticity/Repair
Dual Role for LIM-Homeodomain Gene Lhx2 in the Formation of the Lateral Olfactory Tract

Bhaskar Saha, Padmanabhan Hari, Dhananjay Huilgol, and Shubha Tole

Department of Biological Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai 400 005, India

Correspondence should be addressed to Shubha Tole, Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India. Email: stole{at}tifr.res.in

The development of the olfactory system in vertebrates is a multistep process, in which several regulatory molecules are required at different stages. The development of the olfactory sensory epithelium and its projection to the olfactory bulb are both known to require the LIM-homeodomain transcription factor Lhx2. We examined whether Lhx2 plays a role in the development of the OB itself, as well as its projection to the olfactory cortex.

Although there is no morphological OB protuberance in the Lhx2 mutant, mitral cells are normally specified and cluster in a displaced olfactory bulb-like structure (OBLS). The OBLS is not able to pioneer the lateral olfactory tract (LOT) projection in vivo or when provided control (host) telencephalic territory in an in vitro assay. Strikingly, the mutant OBLS is capable of projecting along the LOT if provided with an existing normal LOT in the host explant. This is the first report of a role for a transcription factor expressed in the OB that selectively affects the axon guidance but not the specification of mitral cells.

Furthermore, the Lhx2 mutant lateral telencephalon does not support growth of an LOT projection from control OB explants. The defect correlates with the disruption of a cellular mechanism that is thought to be critical for LOT pathfinding: a specialized cell population, the "lot cells," is mislocalized in the Lhx2 mutant. In addition, the expression of Sema6A is aberrantly upregulated. Together, these findings reveal a dual role for Lhx2, in the OB as well as in the lateral telencephalon, for establishing the LOT projection.

Key words: axonogenesis; Lhx2; LOT; lot cells; migration; olfactory

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Received April 29, 2006; accepted Jan. 10, 2007.

Correspondence should be addressed to Shubha Tole, Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India. Email: stole{at}tifr.res.in

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				K. Ito, T. Kawasaki, S. Takashima, I. Matsuda, A. Aiba, and T. Hirata Semaphorin 3F Confines Ventral Tangential Migration of Lateral Olfactory Tract Neurons onto the Telencephalon Surface J. Neurosci., April 23, 2008; 28(17): 4414 - 4422. [Abstract] [Full Text] [PDF]

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