Dataset Information

Dual role for LIM-homeodomain gene Lhx2 in the formation of the lateral olfactory tract.

ABSTRACT: 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.

SUBMITTER: Saha B

PROVIDER: S-EPMC2092498 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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Dual role for LIM-homeodomain gene Lhx2 in the formation of the lateral olfactory tract.

Saha Bhaskar B Hari Padmanabhan P Huilgol Dhananjay D Tole Shubha S

The Journal of neuroscience : the official journal of the Society for Neuroscience 20070201 9

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 ...[more]

PMID: 17329426

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Project description:Purpose: Müller glia are the only glial cell type produced by the neuroepithelial progenitor cells which generate the vertebrate retina. Müller glia are required to maintain retinal homeostasis and support the survival of retinal neurons. Furthermore, they function as an adult stem cell, mediating retinal regeneration among select vertebrate classes. However, the mechanisms which regulate Müller development are poorly understood as considerable overlap exists in gene expression between retinal progenitor cells and differentiated Müller glia. We investigate the functional role of the LIM homeodomain transcription factor Lhx2 in the specification and development of Müller glia in the mouse. Methods: RNA-Seq was performed in collaboration with the Johns Hopkins School of Medicine Deep Sequencing and Microarray Core Facility. Libraries were prepared using Illumina TruSeq RNA Sample kit (Illumina, San Diego, CA) following manufacturer’s recommended procedure. The PCR amplified library was purified using RNAClean XP magnetic beads (Agencourt, Beverley, MA) and run out on a High Sensitivity DNA Chip (Agilent, Santa Clara, CA) for quality check. We used STAR to align RNA-Seq reads onto Ensembl mouse genome GRCm38, release 72. To generate the stand attribute for alignments containing splice junctions, we used the outSAMstrandField intronMotif program. The spliced alignments without strand definition were removed. Number of reads mapped to exons was counted by htseq-count. Genes expressed at very low levels were omitted from further analysis. Gene expression differences between wildtype and mutant samples, significance (p-value) and false discovery rate (FDR) were computed using the generalized linear models based EdgeR. Results: We observed a substantial reduction in expression of Notch pathway genes including Notch1, the Notch ligands Dll1 and Dll3, as well as gliogenic Notch effector genes such as Hes1, Hes5, Id1 and Sox8 and the Müller-gliogenic factor Rax. We likewise observe a substantial reduction in expression of progenitor-specific genes such as Vsx2 and Fgf15. Furthermore, we observed a decrease in the expression of early-onset glial markers such as Crym , Spon1, and Car2.

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Dataset Information

Dual role for LIM-homeodomain gene Lhx2 in the formation of the lateral olfactory tract.

Publications

Dual role for LIM-homeodomain gene Lhx2 in the formation of the lateral olfactory tract.

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