MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system - PubMed (original) (raw)

MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system

Marika Kapsimali et al. Genome Biol. 2007.

Abstract

Background: MicroRNA (miRNA) encoding genes are abundant in vertebrate genomes but very few have been studied in any detail. Bioinformatic tools allow prediction of miRNA targets and this information coupled with knowledge of miRNA expression profiles facilitates formulation of hypotheses of miRNA function. Although the central nervous system (CNS) is a prominent site of miRNA expression, virtually nothing is known about the spatial and temporal expression profiles of miRNAs in the brain. To provide an overview of the breadth of miRNA expression in the CNS, we performed a comprehensive analysis of the neuroanatomical expression profiles of 38 abundant conserved miRNAs in developing and adult zebrafish brain.

Results: Our results show miRNAs have a wide variety of different expression profiles in neural cells, including: expression in neuronal precursors and stem cells (for example, miR-92b); expression associated with transition from proliferation to differentiation (for example, miR-124); constitutive expression in mature neurons (miR-124 again); expression in both proliferative cells and their differentiated progeny (for example, miR-9); regionally restricted expression (for example, miR-222 in telencephalon); and cell-type specific expression (for example, miR-218a in motor neurons).

Conclusion: The data we present facilitate prediction of likely modes of miRNA function in the CNS and many miRNA expression profiles are consistent with the mutual exclusion mode of function in which there is spatial or temporal exclusion of miRNAs and their targets. However, some miRNAs, such as those with cell-type specific expression, are more likely to be co-expressed with their targets. Our data provide an important resource for future functional studies of miRNAs in the CNS.

PubMed Disclaimer

Figures

Figure 1

Figure 1

miRNAs expressed in proliferating and/or differentiating cells in the developing and adult zebrafish brain. In this and other figures, unless otherwise mentioned, sections are transverse with dorsal on the top, stage is shown bottom left and miRNA analyzed by in situ hybridization bottom right, in situ staining is in blue and cell nuclei are visualized with nuclear red counterstaining. Abbreviations used in the Results section of the text are denoted in black. For other abbreviations, see Additional data file 26. (a,d,g) miR-92b expression in periventricular and adjacent cells of the telencephalon (a,g), diencephalon and optic tectum (d). (b,e,h) miR-124 expression in differentiating cells in the telencephalon (b,h), diencephalon and optic tectum (e). (c,f,i) miR-9 expression in periventricular/proliferating and differentiating cells of the telencephalon (c,i), diencephalon and optic tectum (f).

Figure 2

Figure 2

Several miRNAs expressed in discrete retinal cell populations. (a-h) Transverse sections through retinae in situ hybridized with miR-92b, let-7b, miR-124, miR-9, miR-183, miR-182, miR-96 and miR-181b probes. Arrows point at proliferative ciliary marginal zone (CMZ) cells in (a,b,d,h). The inset in (e) shows pineal cells. The arrowhead in (g) indicates miR-96 expression in peripheral sensory neuromasts. (i) Confocal section through the retina of a transgenic line Tg(huC:GFP) immunostained for GFP. Other miRNAs with expression in the retina include miR-454a (Figure C in Additional data file 25), miR-132 (Figure E in Additional data file 25), miR-125b (Figure F in Additional data file 25) and miR-181a (Figure G in Additional data file 13).

Figure 3

Figure 3

miR-137 and miR-222 expression is conserved between larval and adult brain. (a,c,e,f) miR-137 expression in the larval caudal telencephalon (a), diencephalon (c), dorsal midbrain (e) and hypothalamus (f). (b,d,g) miR-137 expression in adult brain sections at levels corresponding to the embryonic sections shown in (a), (c) and (e/f), respectively. (h,k) miR-222 expression in the larval telencephalic pallium (P) and subpallium (Sd, Sv), hypothalamus (Hi, TLa, DIL, lr) and posterior tuberculum (PTv, M2). (i,j,l) miR-222 expression in corresponding adult nuclei in the pallium (P, Dm, Dl, Dd, Dc), subpallium (Vd, Vv), hypothalamus (ATN, LH, TLa, DIL, Hd-lr) and posterior tuberculum (nPVO, PGl).

Figure 4

Figure 4

Conserved and divergent expression of miR-181a and miR-181b. (a,b) miR-181a and miR-181b expression in larval tectal (TeO) and migrated pretectal area cells (M1). (c,d) Comparable miR-181a and miR-181b expression in the adult optic tectum (sgz, cz) and pretectal nuclei (PSm, PSp). (e) miR-181a is expressed in more cells than (f) miR-181b (arrowheads) in the adult hypothalamic mamillary body (CM) and dorsal periventricular zone (Hd).

Figure 5

Figure 5

Examples of miRNAs showing differences in expression between larval and adult stages. (a,b) miR-219 expression in the diencephalon at the level of the post-optic commissure (poc) of the larval and adult brain. In the larval brain (a), miR-219 is widely expressed in the ventral (VT) and dorsal (DT) thalamus and periventricular pretectum (Pr) whereas cells of the poc are devoid of expression. In contrast, in the adult (b), miR-219 is expressed in cells in the poc and optic tract (OT) whereas ventrolateral (VL) and ventromedial (VM) thalamic nuclei are devoid of expression. (c-f) miR-34 expression: (c,d) show conserved miR-34 expression in the octaval area (OA, MON, AON, MaON) and Mauthner neuron (MAC) in the larval and adult zebrafish brain, respectively; (e) shows miR-34 in the adult nucleus of the paraventricular organ (nPVO) and the arrow in (f) points to miR-34 expressing cells in the lateral part of the adult left habenula. (g,h) Conserved miR-153a expression throughout the larval (Ha) and adult (Hav, Had) habenulae. (i) miR-137 expression in groups of dorsal habenular cells (Had, arrowheads). (j) miR-138 expression in groups of dorsal habenular cells (Had).

Figure 6

Figure 6

miR-218a is expressed in embryonic cranial and spinal motor-neurons. (a-d,g-h) Larval and adult miR-218a expression in the motor nuclei of the fifth (NV, NVmv), sixth (NVI), seventh (NVII), tenth (NX, NXm) cranial nerves and spinal motor neurons (MN). (e,f) Confocal sagittal sections through the hindbrain of an embryo expressing the Tg(isl1:GFP) transgene with anterior to the left. miR-218a expression is shown in red in (e) and (f) is a superimposition of the miR-218a staining (red) and anti-GFP immunostaining (green). Yellow cells express both miR-218a and GFP in the NVII and NX cranial motor nuclei. (h-j) Additional sites of expression of miR-218a in the adult inferior olive (IO), preoptic magnocellular area (PM) and hypothalamus (Hv, LH).

Similar articles

Cited by

References

    1. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20. doi: 10.1016/j.cell.2004.12.035. - DOI - PubMed
    1. Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B, Rigoutsos I. A pattern-based method for the identification of microRNA binding sites and their corresponding heteroduplexes. Cell. 2006;126:1203–1217. doi: 10.1016/j.cell.2006.07.031. - DOI - PubMed
    1. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425:415–419. doi: 10.1038/nature01957. - DOI - PubMed
    1. Bernstein E, Caudy AA, Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001;409:363–366. doi: 10.1038/35053110. - DOI - PubMed
    1. Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol. 2005;7:719–723. doi: 10.1038/ncb1274. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources