Dystroglycan and mitochondrial ribosomal protein L34 regulate differentiation in the Drosophila eye.
Mutations that diminish the function of the extracellular matrix receptor Dystroglycan (DG) result in muscular dystrophies, with associated neuronal migration defects in the brain and mental retardation e.g. Muscle Eye Brain Disease. To gain insight into the function of DG in the nervous system we initiated a study to examine its contribution to development of the eye of Drosophila melanogaster. Immuno-histochemistry showed that DG is concentrated on the apical surface of photoreceptors (R) cells during specification of cell-fate in the third instar larva and is maintained at this location through early pupal stages. In point mutations that are null for DG we see abortive R cell elongation during differentiation that first appears in the pupa and results in stunted R cells in the adult. Overexpression of DG in R cells results in a small but significant increase in their size. R cell differentiation defects appear at the same stage in a deficiency line Df(2R)Dg(248) that affects Dg and the neighboring mitochondrial ribosomal gene, mRpL34. In the adult, these flies have severely disrupted R cells as well as defects in the lens and ommatidia. Expression of an mRpL34 transgene rescues much of this phenotype. We conclude that DG does not affect neuronal commitment but functions R cell autonomously to regulate neuronal elongation during differentiation in the pupa. We discuss these findings in view of recent work implicating DG as a regulator of cell metabolism and its genetic interaction with mRpL34, a member of a class of mitochondrial genes essential for normal metabolic function.
Zhan
Yougen
Y
Centre for Research in Neuroscience, McGill University Health Centre, Montreal, Quebec, Canada.
Melian
Nadia Y
NY
Pantoja
Mario
M
Haines
Nicola
N
Ruohola-Baker
Hannele
H
Bourque
Charles W
CW
Rao
Yong
Y
Carbonetto
Salvatore
S
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D049030:Dystroglycans / Q000235:genetics* / Q000378:metabolism; D005123:Eye / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D007814:Larva; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D013499:Surface Properties; D019076:Transgenes / Q000235:genetics
D029721:Drosophila Proteins; D024101:Mitochondrial Proteins; D012269:Ribosomal Proteins; C571949:mitochondrial ribosomal protein L34, Drosophila; D049030:Dystroglycans
J Cell Biol. 2002 Jun 24;157(7):1279-90
12082085
J Cell Sci. 2006 Jan 15;119(Pt 2):199-207
16410545
Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12775-80
16908845
FEBS Lett. 2000 Sep 29;482(1-2):13-8
11018515
J Cell Biol. 1999 Jun 14;145(6):1325-40
10366602
Science. 2009 Mar 27;323(5922):1740-3
19325118
Genetics. 1999 Aug;152(4):1631-9
10430588
Development. 1993 Apr;117(4):1223-37
8404527
Dev Biol. 1995 Oct;171(2):415-33
7556924
Mol Biol Cell. 2007 Dec;18(12):4721-30
17881734
J Biol Chem. 2004 Oct 8;279(41):42638-47
15271988
Brain Dev. 2001 Mar;23(2):97-107
11248458
Annu Rev Neurosci. 2008;31:91-123
18333761
Methods Mol Biol. 2008;420:277-87
18641954
J Biol Chem. 2007 May 18;282(20):15159-69
17355978
Proc Natl Acad Sci U S A. 1987 Sep;84(18):6457-61
2957695
Nat Genet. 1999 Nov;23(3):338-42
10610181
Neuromuscul Disord. 2002 Jun;12(5):438-46
12031617
Development. 2003 Jan;130(1):173-84
12441301
Eur J Neurosci. 2006 Jun;23(11):2877-86
16819976
Neuropathol Appl Neurobiol. 2001 Feb;27(1):22-8
11298998
Exp Cell Res. 2005 Jul 15;307(2):354-66
15894314
Nature. 2002 Jul 25;418(6896):422-5
12140559
Nature. 2002 Jul 25;418(6896):417-22
12140558
Cell. 2002 Sep 6;110(5):639-48
12230980
Cell Mol Life Sci. 2006 Jul;63(14):1614-31
16710609
Development. 2006 Oct;133(19):3805-15
16943280
Fly (Austin). 2008 Jan-Feb;2(1):29-35
18820475
Dev Cell. 2005 Dec;9(6):843-54
16326395
Ann Neurol. 2004 Nov;56(5):734-8
15505824
Gene Expr Patterns. 2004 Mar;4(2):153-9
15161095
Dev Biol. 2008 Jan 15;313(2):519-32
18093579
Curr Opin Neurol. 2004 Apr;17(2):205-9
15021250
Neuromuscul Disord. 2002 Oct;12(7-8):623-30
12207929
Mech Dev. 2006 Mar;123(3):228-40
16458488
Dev Cell. 2009 Jan;16(1):83-92
19154720
EMBO J. 2007 Jan 24;26(2):481-93
17215867
Nat Protoc. 2006;1(6):2635-42
17406519
Science. 1994 Aug 5;265(5173):785-9
7914031
Nature. 1969 Apr 26;222(5191):354-6
5782111
J Cell Biol. 1993 Aug;122(4):809-23
8349731
Cell Metab. 2005 Jan;1(1):15-25
16054041
J Biol Chem. 1988 Oct 15;263(29):14964-9
2971661
Genetics. 2006 Sep;174(1):525-33
16849596
Results Probl Cell Differ. 2000;31:15-36
10929399
Nat Clin Pract Neurol. 2006 Apr;2(4):222-30
16932553
Dev Cell. 2001 Nov;1(5):717-24
11709191
Development. 2006 Aug;133(16):3245-54
16873583
Ann Neurol. 2006 Jul;60(1):137-44
16642511
Glycobiology. 2010 Mar;20(3):381-94
19969597