Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis.
BACKGROUND
Cortical development is a complex process that includes sequential generation of neuronal progenitors, which proliferate and migrate to form the stratified layers of the developing cortex. To identify the individual microRNAs (miRNAs) and mRNAs that may regulate the genetic network guiding the earliest phase of cortical development, the expression profiles of rat neuronal progenitors obtained at embryonic day 11 (E11), E12 and E13 were analyzed.


RESULTS
Neuronal progenitors were purified from telencephalic dissociates by a positive-selection strategy featuring surface labeling with tetanus-toxin and cholera-toxin followed by fluorescence-activated cell sorting. Microarray analyses revealed the fractions of miRNAs and mRNAs that were up-regulated or down-regulated in these neuronal progenitors at the beginning of cortical development. Nearly half of the dynamically expressed miRNAs were negatively correlated with the expression of their predicted target mRNAs.


CONCLUSIONS
These data support a regulatory role for miRNAs during the transition from neuronal progenitors into the earliest differentiating cortical neurons. In addition, by supplying a robust data set in which miRNA and mRNA profiles originate from the same purified cell type, this empirical study may facilitate the development of new algorithms to integrate various "-omics" data sets.
Nielsen
Joseph A
JA
Section of Developmental Genetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. joseph.nielsen@fda.hhs.gov
Lau
Pierre
P
Maric
Dragan
D
Barker
Jeffery L
JL
Hudson
Lynn D
LD
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002469:Cell Separation; D002478:Cells, Cultured; D019295:Computational Biology; D015536:Down-Regulation; D005260:Female; D005333:Fetus; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics*; D039902:Multipotent Stem Cells / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013687:Telencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015854:Up-Regulation
D035683:MicroRNAs; D012333:RNA, Messenger
Nature. 2005 Dec 1;438(7068):671-4
16319892
Nucleic Acids Res. 2006 Jan 24;34(2):e9
16434699
Nucleic Acids Res. 2003 Jan 1;31(1):82-6
12519953
Curr Opin Neurobiol. 2006 Feb;16(1):25-34
16426837
Mol Cell Biol. 2005 Jul;25(13):5699-711
15964824
J Neurosci. 2000 Nov 1;20(21):8042-50
11050125
Science. 2005 Dec 16;310(5755):1817-21
16308420
Genome Biol. 2003;4(3):R22
12620107
Curr Protoc Neurosci. 2005 Nov;Chapter 3:Unit 3.18
18428621
J Neurosci. 2002 Mar 1;22(5):1583-91
11880488
Nucleic Acids Res. 2002 May 1;30(9):e36
11972351
Nat Rev Genet. 2004 May;5(5):396-400
15143321
Mol Cell. 2007 Jul 6;27(1):91-105
17612493
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D562-6
15608262
Stem Cells. 2006 Apr;24(4):857-64
16357340
Science. 2004 Apr 23;304(5670):594-6
15105502
Nat Rev Neurosci. 2007 Jun;8(6):427-37
17514196
Dev Biol. 2005 Jul 15;283(2):269-81
15890332
Eur J Neurosci. 2006 Feb;23(4):857-68
16519651
Cell. 1993 Dec 3;75(5):843-54
8252621
Neuron. 2005 Jan 20;45(2):207-21
15664173
J Neurosci. 2007 Feb 21;27(8):1836-52
17314281
Genome Biol. 2004;5(9):R68
15345052
Genome Biol. 2003;4(5):P3
12734009
Science. 1997 Oct 17;278(5337):474-6
9334308
Science. 2004 Dec 24;306(5705):2255-7
15618518
RNA. 2003 Oct;9(10):1274-81
13130141
Dev Neurosci. 2008;30(1-3):117-31
18075260
Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2746-51
16477010
Neuron. 1995 Jun;14(6):1141-52
7605629
Nat Methods. 2004 Oct;1(1):47-53
15782152
Cereb Cortex. 2007 Sep;17(9):2108-22
17150988
Cereb Cortex. 2000 Apr;10(4):400-12
10769250
Dev Cell. 2003 Aug;5(2):351-8
12919684
Science. 2007 Dec 21;318(5858):1931-4
18048652
Cereb Cortex. 2000 Aug;10(8):729-47
10920046
Annu Rev Cell Dev Biol. 2007;23:175-205
17506695
Mol Cell. 2007 Jun 8;26(5):753-67
17560377
Cell. 2004 Jan 23;116(2):281-97
14744438
EMBO J. 2008 Feb 6;27(3):471-81
18256698
Genes Dev. 2007 Apr 1;21(7):744-9
17403776
J Neurosci. 2003 Jan 1;23(1):240-51
12514221