Islet‐1 expression in the developing chicken inner earLi, Huawei; Liu, Hong; Sage, Cyrille; Huang, Mingqian; Chen, Zheng‐Yi; Heller, Stefan
doi: 10.1002/cne.20190pmid: 15281076
The cell types of the inner ear originate from the otic placode, a thickened layer of ectoderm adjacent to the developing hindbrain. The placode invaginates and forms the otic pit, which pinches off as a small vesicle called the otocyst. Presumptive cochleovestibular neurons delaminate from the anterior ventral part of the otocyst and form the cochleovestibular ganglion of the inner ear. Here we show that the LIM/homeodomain protein islet‐1 is expressed in cells of the ventral part of the otic placode and that this ventral expression is maintained at the otic pit and the otocyst stages. Auditory and vestibular neurons originate from this islet‐1‐positive zone of the otocyst, and these neurons maintain islet‐1 expression until adulthood. We also demonstrate that islet‐1 becomes up‐regulated in the presumptive sensory epithelia of the inner ear in regions that are defined by the expression domains of BMP4. The up‐regulation of islet‐1 in developing inner ear hair and supporting cells is accompanied by down‐regulation of Pax‐2 in these cell types. Islet‐1 expression in hair and supporting cells persists until early postnatal stages, when the transcriptional regulator is down‐regulated in hair cells. Our data is consistent with a role for islet‐1 in differentiating inner ear neurons and sensory epithelia cells, perhaps in the specification of cellular subtypes in conjunction with other LIM/homeodomain proteins. J. Comp. Neurol. 477:1–10, 2004. © 2004 Wiley‐Liss, Inc.
ERp29, a general endoplasmic reticulum marker, is highly expressed throughout the brainMacLeod, Jennifer C.; Sayer, Rod J.; Lucocq, John M.; Hubbard, Michael J.
doi: 10.1002/cne.20222pmid: 15281078
ERp29 is a recently discovered resident of the endoplasmic reticulum (ER) that is abundant in brain and most other mammalian tissues. Investigations of nonneural secretory tissues have implicated ERp29 in a major role producing export proteins, but a molecular activity remains wanting for this functional orphan. Intriguingly, ERp29 appears to be heavily utilized in the cerebellum, a brain region not conventionally regarded as neurosecretory. To elucidate this functional quandary, we used immunochemical approaches to characterize the regional, cellular, and subcellular distributions of ERp29 in rat brain. Immunohistochemistry revealed ubiquitous expression in neuronal and nonneuronal cells, with a distinctive variation in somatic ERp29 levels. Highly expressing cells were found in diverse locations, implying that ERp29 is not biased towards the cerebellum functionally. Using immunolocalization data mined from the literature, a proteomic profile was developed to assess the functional significance of ERp29's characteristic expression pattern. Surprisingly, ERp29 correlated poorly with classical markers of neurosecretion, but strongly with a variety of major membrane proteins. Together with immunogold localization of ERp29 to somatic ER, these observations led to a novel hypothesis that ERp29 is involved primarily in production of endomembrane proteins rather than proteins destined for export. This study establishes ERp29 as a general ER marker for brain cells and provides a stimulating clue about ERp29's enigmatic function. ERp29 appears to have broad significance for neural pathophysiology, given its ubiquitous distribution and prominence in brain over classical ER residents like BiP and protein disulfide isomerase. J. Comp. Neurol. 477:29–42, 2004. © 2004 Wiley‐Liss, Inc.
Fiber order of the normal and regenerated optic tract of the frog (Rana pipiens)Bach, Helene; Arango, Victoria; Feldheim, David; Flanagan, John G.; Scalia, Frank
doi: 10.1002/cne.20238pmid: 15281079
In the normal frog, axons from the peripheral retina arising at the temporal pole course superficially in the middle stream of the diencephalic optic tract. Axons from the nasal pole course in two streams running in the opposite margins of the tract, dorsonasal axons ventrally, ventronasal axons dorsally. Axons from the dorsal and ventral poles of the retina occupy the intervals between the aforementioned middle and marginal streams. Axons from more central regions of the retina tend to occupy deeper levels of the optic tract. The regenerated optic tract does not regain its normal organization, e.g., axons of peripheral nasal origin are spread out widely over the entire width of the tract. However, axons from the temporal pole of the retina do return approximately to their original location in the middle stream. The concentration of temporal axons in the middle stream of the optic tract after regeneration may now be understood in terms of the expression pattern of the ephrin‐A class of receptor tyrosine kinase ligands in the cellular matrix of the optic tract. The ephrin‐As, which have a repellent effect on growing temporal retinal axons, are concentrated in and along the margins of the diencephalic optic tract and essentially absent from its middle stream. It is proposed here that peripheral temporal axons may be forced into this middle region by their avoidance of the higher levels of ephrin‐A expression in the tract margins. In contrast, the growth pattern of regenerating peripheral nasal axons would not be affected by the ephrin‐A gradient in the optic tract. J. Comp. Neurol. 477:43–54, 2004. © 2004 Wiley‐Liss, Inc.
Expression of regulatory genes during differentiation of thalamic nuclei in mouse and monkeyJones, Edward G.; Rubenstein, John L.R.
doi: 10.1002/cne.20234pmid: 15281080
Expression patterns of genes implicated in development of the thalamus were examined in mice and monkeys, using in situ hybridization with RNA probes complementary to Cad6, Dlx1, Dlx2, Dlx5, Gbx2, Id2, and Lef1 cDNAs. Expression patterns were related to the evolving cytoarchitecture in mice at birth (P0) and in adulthood, and in fetal monkeys early and late in the period of gestation when thalamic nuclei are becoming histologically differentiated out of a series of pronuclear masses. At the earlier developmental stage, each gene was expressed in a pattern that appeared to be pronucleus‐specific and maintained a nucleus‐specific pattern into adulthood, with the possible exception of Gbx2. Each gene displayed a unique expression pattern in the dorsal thalamus, ventral thalamus, and epithalamus, and no gene was expressed throughout all three divisions or in every nucleus of a division. With the exception of Dlx2, whose expression disappeared at the later time point, all continued to be expressed into adulthood at higher levels and with identical patterns. Despite late appearance of γ‐aminobutyric acid (GABA)ergic cells in the dorsal lateral geniculate nucleus of mice, no Dlx genes, which promote formation of a GABAergic phenotype elsewhere, were detected in dorsal thalamus. Each thalamic nucleus was distinguished by expression of a combination of genes, and homologous nuclei in mouse and monkey exhibited the same combination. The presence of a centre médian nucleus and four pulvinar nuclei in monkeys was marked by patterns of expression not found in mice. The centre médian nucleus was marked by high expression of Id2, which was expressed only weakly in very few nuclei of mice. J. Comp. Neurol. 477:55–80, 2004. © 2004 Wiley‐Liss, Inc.
Laminar organization of the mouse dentate gyrus: Insights from BETA2/Neuro D mutant miceDel Turco, Domenico; Gebhardt, Carl; Burbach, Guido J.; Pleasure, Samuel J.; Lowenstein, Daniel H.; Deller, Thomas
doi: 10.1002/cne.20239pmid: 15281081
The dentate gyrus of rodents is characterized by a highly laminar organization: above a compact granule cell layer, commissural/associational (C/A) fibers terminate on proximal granule cell dendrites and entorhinal fibers terminate on distal granule cell dendrites in a nonoverlapping manner. To gain insights into mechanisms that underlie the formation of this laminar structure, we studied mice deficient for BETA2/NeuroD, a basic helix‐loop‐helix transcription factor essential for granule cell differentiation. Anterograde tracing was used to label C/A and entorhinal fibers and combined with confocal double immunofluorescence for calbindin, calretinin, parvalbumin, and reelin to visualize putative target cells. The dentate gyrus of mutant mice contained only few granule cells, which formed a cap‐like structure adjacent to area CA3. Despite the severe hypoplasia of the dentate gyrus, the remaining BETA2/NeuroD‐deficient granule cells expressed mature markers, extended dendrites into the molecular layer, and extended mossy fibers into area CA3. Entorhinal and C/A fibers terminated in a nonoverlapping manner in the dendritic field overlying the rudiment. Entorhinal fibers terminated in the outermost portion of the dentate gyrus where they surrounded reelin‐positive Cajal–Retzius cells, and C/A fibers terminated above and within the dentate rudiment. The laminar termination of C/A fibers was closest to normal in zones of the rudiment in which granule cells were densely packed. These data indicate that granule cells are able to differentiate in the absence of BETA2/NeuroD and suggest that the signals underlying the laminar anatomy of the dentate gyrus are present in the absence of most target cells. J. Comp. Neurol. 477:81–95, 2004. © 2004 Wiley‐Liss, Inc.
Genetic control of sensitivity to hippocampal cell death induced by kainic acid: A quantitative trait loci analysisSchauwecker, Paula Elyse; Williams, Robert W.; Santos, Julia Belen
doi: 10.1002/cne.20245pmid: 15281082
Host genetic factors are likely to contribute to differences in individual susceptibility to seizure‐induced excitotoxic neuronal damage. Similarly, inbred strains of mice differ in their susceptibility to the kainic acid (KA) model of seizure‐induced cell death, but the genes responsible for the differences are not known. Here, we define the inheritance patterns of susceptibility to KA‐induced neurodegeneration in the hippocampus by assessing 331 back‐cross (N2) progeny of two inbred mouse strains, C57BL/6 and FVB/N, previously shown to display resistance and sensitivity to KA‐induced cell death, respectively. Results of phenotypic analysis suggest that the difference in susceptibility between these two strains is conferred by a single dominant gene. Therefore, we used an N2 back‐cross between the inbred C57BL/6 and FVB/N strains for a genome‐wide search for quantitative trait loci (QTLs), which are chromosomal sites containing genes influencing the magnitude of susceptibility. Genome‐wide interval mapping in N2 progeny identified a locus on distal chromosome (Chr) 18 with a peak LOD score of 4.9 localized between D18Mit186 and D18Mit4 as having the strongest and most significant effect in this model. QTLs of minor effect were detected on Chr 15 (D15Mit174‐D15Mit156) and Chr 4 (D4Mit264‐D4Mit91), with peak LOD scores of 3.02 and 2.46, respectively. The three significant QTLs (Chrs 4, 15, 18) together account for nearly 25% of the trait variance for both genders combined. Reduced KA‐induced cell death susceptibility was observed in a congenic strain in which the highly susceptible FVB/N strain carried putative resistance alleles from the C57BL/6 strain on Chr 18. J. Comp. Neurol. 477:96–107, 2004. © 2004 Wiley‐Liss, Inc.
The basic helix‐loop‐helix transcription factor neuroD is expressed in the rod lineage of the teleost retinaHitchcock, Peter; Kakuk‐Atkins, Laura
doi: 10.1002/cne.20244pmid: 15281083
Persistent rod genesis in the retinas of teleost fish was first described over 2 decades ago, but little is known regarding the underlying genetic and molecular mechanisms that govern this phenomenon. Because of its function in the developing mammalian retina and persistently mitotic adult tissues, we sought to characterize the cellular expression of the basic helix‐loop‐helix (bHLH) transcription factor neuroD in the persistently neurogenic retina of adult teleosts. We show here that, in the adult retina of the goldfish, neuroD is expressed by putative amacrine cells, nascent cones, and the mitotically active cells of the rod lineage. neuroD is the first gene shown to be expressed by rod precursors, the immediate antecedents of rod photoreceptors. In contrast to the vertebrate classes described previously, neuroD is not expressed in multipotent progenitors in the teleost retina. Combining neuroD in situ hybridizations with cell‐cycle‐specific markers suggests that, in rod precursors, neuroD expression is cell cycle specific. J. Comp. Neurol. 477:108–117, 2004. © 2004 Wiley‐Liss, Inc.