A zebrafish LMO4 ortholog limits the size of the forebrain and eyes through negative regulation of six3b and rx3.
The Six3 and Rx3 homeodomain proteins are essential for the specification and proliferation of forebrain and retinal precursor cells of the vertebrate brain, and the regulatory networks that control their expression are beginning to be elucidated. We identify the zebrafish lmo4b gene as a negative regulator of forebrain growth that acts via restriction of six3 and rx3 expression during early segmentation stages. Loss of lmo4b by morpholino knockdown results in enlargement of the presumptive telencephalon and optic vesicles and an expansion of the post-gastrula expression domains of six3 and rx3. Overexpression of lmo4b by mRNA injection causes complementary phenotypes, including a reduction in the amount of anterior neural tissue, especially in the telencephalic, optic and hypothalamic primordia, and a dosage-sensitive reduction in six3 and rx3 expression. We suggest that lmo4b activity is required at the neural boundary to restrict six3b expression, and later within the neural plate to for attenuation of rx3 expression independently of its effect on six3 transcription. We propose that lmo4b has an essential role in forebrain development as a modulator of six3 and rx3 expression, and thus indirectly influences neural cell fate commitment, cell proliferation and tissue growth in the anterior CNS.
McCollum
Catherine W
CW
Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
Amin
Shivas R
SR
Pauerstein
Philip
P
Lane
Mary Ellen
ME
D000595:Amino Acid Sequence; D000818:Animals; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D005123:Eye / Q000196:embryology / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016548:Prosencephalon / Q000196:embryology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*; D000097607:Homeobox Protein SIX3
D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000097607:Homeobox Protein SIX3; C525393:LMO4b protein, zebrafish; C488383:Rx3 protein, zebrafish
Development. 2002 Sep;129(17):4057-63
12163408
Dev Dyn. 2006 Oct;235(10):2811-6
16894600
Genes Dev. 2003 Feb 1;17(3):368-79
12569128
Mol Cell Neurosci. 2003 Jan;22(1):25-36
12595236
Biochem Biophys Res Commun. 2003 Aug 8;307(4):891-9
12878195
Development. 2003 Nov;130(21):5155-67
12944429
Development. 2003 Nov;130(21):5143-54
12975341
EMBO Rep. 2003 Sep;4(9):894-9
12947416
Mech Dev. 2002 Dec;119 Suppl 1:S185-9
14516683
Dev Cell. 2004 Feb;6(2):167-81
14960272
Mol Cell Biol. 2004 Mar;24(5):2063-73
14966285
Mol Cell Biol. 2004 Mar;24(5):2074-82
14966286
Nature. 2004 Feb 19;427(6976):745-9
14973488
Genes Dev. 1999 Dec 1;13(23):3106-14
10601036
Development. 2000 May;127(9):1911-9
10751179
Biochim Biophys Acta. 2000 Apr 25;1491(1-3):240-7
10760585
Cell Mol Life Sci. 2000 Feb;57(2):186-94
10766016
Mech Dev. 2000 Jul;95(1-2):267-70
10906475
Dev Biol. 2001 Mar 1;231(1):13-30
11180949
Dev Dyn. 2001 Apr;220(4):402-8
11307172
Dev Biol. 2001 Apr 15;232(2):315-26
11401394
Dev Dyn. 2001 Jul;221(3):342-9
11458394
Development. 2001 Oct;128(20):4035-44
11641226
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14452-7
11734645
Oncogene. 2004 Feb 26;23(8):1507-13
14676840
Dev Biol. 2004 Jun 15;270(2):336-49
15183718
Mech Dev. 2004 Oct;121(10):1189-97
15327780
J Neurosci. 1994 Jun;14(6):3475-86
7911517
Development. 1996 Jun;122(6):1873-83
8674426
Development. 1998 Aug;125(15):2973-82
9655819
Development. 1998 Aug;125(15):2983-93
9655820
Development. 1998 Nov;125(22):4403-16
9778500
Mech Dev. 1998 Oct;77(2):185-96
9831649
Genes Dev. 1999 Mar 15;13(6):649-54
10090721
Mech Dev. 1999 Jun;84(1-2):195-8
10473141
Int J Dev Biol. 2004;48(8-9):761-70
15558469
Mol Cell Neurosci. 2005 Feb;28(2):205-14
15691703
J Histochem Cytochem. 2005 Apr;53(4):475-86
15805422
Development. 2005 May;132(10):2401-13
15843413
Oncogene. 2005 Jul 14;24(30):4820-8
15856027
Dev Biol. 2005 Nov 15;287(2):456-68
16226737
Dev Biol. 2005 Dec 15;288(2):348-62
16300752
Curr Opin Neurobiol. 2006 Feb;16(1):5-12
16418000
Biochem Biophys Res Commun. 2006 May 19;343(4):1186-90
16580634
Development. 2006 Aug;133(15):2925-35
16818451
Science. 2006 Aug 25;313(5790):1130-4
16931763
Development. 2006 Oct;133(19):3895-905
16943271
Development. 2003 Jan;130(1):185-95
12441302