No abstract

To visualize and isolate live dopamine (DA)-producing neurons in the embryonic ventral mesencephalon, we generated transgenic mice expressing green fluorescent protein (GFP) under the control of the rat tyrosine hydroxylase gene promoter. In the transgenic mice, GFP expression was observed in the developing DA neurons containing tyrosine hydroxylase. The outgrowth and cue-dependent guidance of GFP-labeled axons was monitored in vitro with brain culture systems. To isolate DA neurons expressing GFP from brain tissue, cells with GFP fluorescence were sorted by fluorescence-activated cell sorting. More than 60% of the sorted GFP ؉ cells were positive for tyrosine hydroxylase, confirming that the population had been successfully enriched with DA neurons. The sorted GFP ؉ cells were transplanted into a rat model of Parkinson's disease. Some of these cells survived and innervated the host striatum, resulting in a recovery from Parkinsonian behavioral defects. This strategy for isolating an enriched population of DA neurons should be useful for cellular and molecular studies of these neurons and for clinical applications in the treatment of Parkinson's disease.

Many members of the forkhead/winged helix transcriptional factors are known to be regulators of embryogenesis. Mutations of the Fox gene family have been implicated in a range of human developmental disorders. Foxp2, a member of the Fox gene family, has recently been identified as the first gene that is linked to an inherited form of language and speech disorder. To elucidate the anatomical basis of language processing in the brain, we have examined the expression pattern of Foxp2 gene and its homologous gene, Foxp1, in the rat brain through development. Expression of Foxp2 mRNA was detected in the ventral telencephalon as early as embryonic day 13. Foxp2 mRNA was expressed primarily in differentiated cells of the lateral ganglionic eminence (striatal primordium). Of particular interest was that the developmental expression of Foxp2 followed a compartmental order in the striatum. Patches containing high levels of Foxp2 were aligned with patches enriched in mu-opoid receptor, a marker for striosomal cells, in the striatum through postnatal development. Conversely, Foxp2-positive patches were devoid of calbindin-D28k, a maker for striatal matrix cells. Therefore, Foxp2 was preferentially expressed in striosomal compartment in the striatum during development. In the mature striatum, Foxp2 expression was maintained in striosomes, although its expression level was reduced. In contrast to Foxp2, Foxp1 was expressed in both the striosomal and matrix compartments in the striatum through development. The striatum is known to be involved in the process of procedural memory, and mutation of Foxp2 results in neurological disorders of language and speech. Given the preferential expression of Foxp2 in the striosomal compartment, the striatum, particularly the striosomal system, may participate in neural information processing for language and speech. Our suggestion is consistent with the declarative/procedural model proposed by Ullman and colleagues (Ullman et al. [1997] J. Cogn. Neurosci. 9:266-276; Ullman [2001] Nat. Rev. Neurosci. 2:717-726), in which the procedural memory-dependent mental grammar is rooted in the basal ganglia and the frontal cortex and the declarative memory-dependent mental lexicon is rooted in the temporal lobe.

Colonization of new ecological niches has triggered large adaptive radiations. Although some lineages have made use of such opportunities, not all do so. The factors causing this variation among lineages are largely unknown. Here, we show that deficiency in docosahexaenoic acid (DHA), an essential ω-3 fatty acid, can constrain freshwater colonization by marine fishes. Our genomic analyses revealed multiple independent duplications of the fatty acid desaturase gene Fads2 in stickleback lineages that subsequently colonized and radiated in freshwater habitats, but not in close relatives that failed to colonize. Transgenic manipulation of Fads2 in marine stickleback increased their ability to synthesize DHA and survive on DHA-deficient diets. Multiple freshwater ray-finned fishes also show a convergent increase in Fads2 copies, indicating its key role in freshwater colonization.