Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development.

To characterize temporal patterns of transcriptional activity during normal lung development, we generated genome wide gene expression data for 26 pre- and post-natal time points in three common inbred strains of laboratory mice (C57BL/6J, A/J, and C3H/HeJ). Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression. The 4,683 genes contributing to the strain-independent expression patterns were used to define a murine Developing Lung Characteristic Subtranscriptome (mDLCS). Regression modeling of the Principal Components supported the four canonical stages of mammalian embryonic lung development (embryonic, pseudoglandular, canalicular, saccular) defined previously by morphology and histology. For postnatal alveolar development, the regression model was consistent with four stages of alveolarization characterized by episodic transcriptional activity of genes related to pulmonary vascularization. Genes expressed in a strain-dependent manner were enriched for annotations related to neurogenesis, extracellular matrix organization, and Wnt signaling. Finally, a comparison of mouse and human transcriptomics from pre-natal stages of lung development revealed conservation of pathways associated with cell cycle, axon guidance, immune function, and metabolism as well as organism-specific expression of genes associated with extracellular matrix organization and protein modification. The mouse lung development transcriptome data generated for this study serves as a unique reference set to identify genes and pathways essential for normal mammalian lung development and for investigations into the developmental origins of respiratory disease and cancer. The gene expression data are available from the Gene Expression Omnibus (GEO) archive (GSE74243). Temporal expression patterns of mouse genes can be investigated using a study specific web resource (http://lungdevelopment.jax.org).

Quantitative analysis of the bilateral brainstem projections from the whisker and forepaw regions in rat primary motor cortex.

The whisker region in rat primary motor (MI) cortex projects to several brainstem regions, but the relative strength of these projections has not been characterized. We recently quantified the MI projections to bilateral targets in the forebrain (Alloway et al. [2009] J Comp Neurol 515:548-564), and the present study extends those findings by quantifying the MI projections to bilateral targets in the brainstem. We found that both the whisker and forepaw regions in MI project most strongly to the basal pons and superior colliculus. While the MI forepaw region projects mainly to the ipsilateral basilar pons, the MI whisker region has significantly more connections with the contralateral side. This bilateral difference suggests that corticopontine projections from the MI whisker region may have a role in coordinating bilateral whisker movements. Anterograde tracer injections in MI did not reveal any direct projections to the facial nucleus, but retrograde tracer injections in the facial nucleus revealed some labeled neurons in MI cortex. The number of retrogradely labeled neurons in MI, however, was dwarfed by a much larger number of labeled neurons in the superior colliculus and other brainstem regions. Together, our anterograde and retrograde tracing results indicate that the superior colliculus provides the most effective route for transmitting information from MI to the facial nucleus.

Bilateral projections from rat MI whisker cortex to the neostriatum, thalamus, and claustrum: forebrain circuits for modulating whisking behavior.

In rats, whisking behavior is characterized by high-frequency synchronous movements and other stereotyped patterns of bilateral coordination that are rarely seen in the bilateral movements of the limbs. This suggests that the motor systems controlling whisker and limb movements must have qualitative or quantitative differences in their interhemispheric connections. To test this hypothesis, anterograde tracing methods were used to characterize the bilateral distribution of projections from the whisker and forepaw regions in the primary motor (MI) cortex. Unilateral tracer injections in the MI whisker or forepaw regions revealed robust projections to the corresponding MI cortical area in the contralateral hemisphere. Both MI regions project bilaterally to the neostriatum, but the corticostriatal projections from the whisker region are denser and more evenly distributed across both hemispheres than those from the MI forepaw region. The MI whisker region projects bilaterally to several nuclei in the thalamus, whereas the MI forepaw region projects almost exclusively to the ipsilateral thalamus. The MI whisker region sends dense projections to the contralateral claustrum, but those to the ipsilateral claustrum are less numerous. By contrast, the MI forepaw region sends few projections to the claustrum of either hemisphere. Bilateral deposits of different tracers in MI revealed overlapping projections to the neostriatum, thalamus, and claustrum when the whisker regions were injected, but not when the forepaw regions were injected. These results suggest that the bilateral coordination of the whiskers depends, in part, on MI projections to the contralateral neostriatum, thalamus, and claustrum.