title: Daam1a mediates asymmetric habenular morphogenesis by regulating dendritic and axonal outgrowth.
abstract: Although progress has been made in resolving the genetic pathways that specify neuronal asymmetries in the brain, little is known about genes that mediate the development of structural asymmetries between neurons on left and right. In this study, we identify daam1a as an asymmetric component of the signalling pathways leading to asymmetric morphogenesis of the habenulae in zebrafish. Daam1a is a member of the Formin family of actin-binding proteins and the extent of Daam1a expression in habenular neuron dendrites mirrors the asymmetric growth of habenular neuropil between left and right. Local loss and gain of Daam1a function affects neither cell number nor subtype organisation but leads to a decrease or increase of neuropil, respectively. Daam1a therefore plays a key role in the asymmetric growth of habenular neuropil downstream of the pathways that specify asymmetric cellular domains in the habenulae. In addition, Daam1a mediates the development of habenular efferent connectivity as local loss and gain of Daam1a function impairs or enhances, respectively, the growth of habenular neuron terminals in the interpeduncular nucleus. Abrogation of Daam1a disrupts the growth of both dendritic and axonal processes and results in disorganised filamentous actin and α-tubulin. Our results indicate that Daam1a plays a key role in asymmetric habenular morphogenesis mediating the growth of dendritic and axonal processes in dorsal habenular neurons.
authors.affiliation: Institute of Biomedical Sciences, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile.
authors.forename: Alicia
authors.initials: A
authors.lastname: Colombo
authors.forename: Karina
authors.initials: K
authors.lastname: Palma
authors.forename: Lorena
authors.initials: L
authors.lastname: Armijo
authors.forename: Marina
authors.initials: M
authors.lastname: Mione
authors.forename: Iskra A
authors.initials: IA
authors.lastname: Signore
authors.forename: Camila
authors.initials: C
authors.lastname: Morales
authors.forename: Néstor
authors.initials: N
authors.lastname: Guerrero
authors.forename: Margarita M
authors.initials: MM
authors.lastname: Meynard
authors.forename: Ramón
authors.initials: R
authors.lastname: Pérez
authors.forename: José
authors.initials: J
authors.lastname: Suazo
authors.forename: Katherine
authors.initials: K
authors.lastname: Marcelain
authors.forename: Luis
authors.initials: L
authors.lastname: Briones
authors.forename: Steffen
authors.initials: S
authors.lastname: Härtel
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wilson
authors.forename: Miguel L
authors.initials: ML
authors.lastname: Concha
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D003712:Dendrites / Q000378:metabolism*; D019262:Habenula / Q000196:embryology* / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins
keywords: Asymmetry; Daam1; Habenula; Morphogenesis; Nervous system; Zebrafish
references.citation: Trends Cell Biol. 2003 Aug;13(8):435-46
references.pmid: 12888296
references.citation: Gene. 1983 Nov;25(2-3):263-9
references.pmid: 6198242
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6708-13
references.pmid: 17412835
references.citation: Neurosci Lett. 2008 Dec 5;447(1):62-7
references.pmid: 18832009
references.citation: PLoS One. 2011 Mar 28;6(3):e18340
references.pmid: 21464901
references.citation: Genes Dev. 2008 Dec 1;22(23):3292-307
references.pmid: 19056884
references.citation: Nat Protoc. 2008;3(1):59-69
references.pmid: 18193022
references.citation: Neuron. 2000 Nov;28(2):399-409
references.pmid: 11144351
references.citation: Development. 2000 Mar;127(5):1081-93
references.pmid: 10662647
references.citation: Philos Trans R Soc Lond B Biol Sci. 2009 Apr 12;364(1519):991-1003
references.pmid: 19064351
references.citation: Dev Dyn. 2004 Oct;231(2):449-59
references.pmid: 15366023
references.citation: J Comp Neurol. 2007 Jun 1;502(4):611-9
references.pmid: 17394162
references.citation: Neuron. 2003 Jul 31;39(3):423-38
references.pmid: 12895418
references.citation: Neural Dev. 2007 Mar 15;2:6
references.pmid: 17359546
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):6906-11
references.pmid: 20351293
references.citation: Philos Trans R Soc Lond B Biol Sci. 2009 Apr 12;364(1519):1005-20
references.pmid: 19064356
references.citation: Curr Biol. 2010 Dec 21;20(24):2211-6
references.pmid: 21145744
references.citation: Development. 2003 Mar;130(6):1059-68
references.pmid: 12571098
references.citation: Genes Dev. 2001 Jun 1;15(11):1427-34
references.pmid: 11390362
references.citation: Neuron. 2002 May 16;34(4):577-88
references.pmid: 12062041
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):210-5
references.pmid: 18162551
references.citation: Front Neurosci. 2011 Dec 21;5:138
references.pmid: 22203792
references.citation: Neuron. 2007 Aug 2;55(3):393-405
references.pmid: 17678853
references.citation: J Neurosci. 2008 Dec 3;28(49):13310-9
references.pmid: 19052223
references.citation: Nat Rev Neurosci. 2012 Dec;13(12):832-43
references.pmid: 23165260
references.citation: Methods Mol Biol. 2009;546:145-51
references.pmid: 19378103
references.citation: Neuroreport. 2004 Aug 26;15(12):1843-6
references.pmid: 15305121
references.citation: J Anat. 2001 Jul-Aug;199(Pt 1-2):63-84
references.pmid: 11523830
references.citation: Cell. 2001 Dec 28;107(7):843-54
references.pmid: 11779461
references.citation: Nat Protoc. 2008;3(6):1101-8
references.pmid: 18546601
references.citation: Development. 1999 Jun;126(14):3253-62
references.pmid: 10375514
references.citation: Development. 2003 Jun;130(11):2303-16
references.pmid: 12702646
references.citation: Neural Dev. 2008 Mar 31;3:9
references.pmid: 18377638
references.citation: Dev Dyn. 1995 Jul;203(3):253-310
references.pmid: 8589427
references.citation: Curr Opin Neurobiol. 2010 Oct;20(5):572-7
references.pmid: 20554443
references.citation: Dev Cell. 2007 Jan;12(1):87-98
references.pmid: 17199043
references.citation: Dev Neurobiol. 2012 Mar;72(3):395-403
references.pmid: 22328274
references.citation: Commun Integr Biol. 2011 Sep;4(5):538-42
references.pmid: 22046456
references.citation: Genesis. 2001 Jul;30(3):175-7
references.pmid: 11477701
references.citation: Genes Brain Behav. 2009 Jul;8(5):500-11
references.pmid: 19496826
references.citation: Development. 2006 Mar;133(5):957-66
references.pmid: 16469972
references.citation: Development. 1998 Jul;125(13):2381-95
references.pmid: 9609821
references.citation: Development. 2007 Feb;134(4):647-58
references.pmid: 17259302
references.citation: Curr Biol. 2005 Feb 8;15(3):238-43
references.pmid: 15694307
references.citation: Semin Cell Dev Biol. 2009 Jun;20(4):498-509
references.pmid: 19560050
references.citation: Neuron. 2009 Jan 15;61(1):27-34
references.pmid: 19146810
references.citation: Genes Dev. 2004 Mar 1;18(5):541-58
references.pmid: 15014045
references.citation: J Neurosci. 2011 Jul 6;31(27):9869-78
references.pmid: 21734278
references.citation: Nat Neurosci. 2010 Nov;13(11):1354-6
references.pmid: 20935642
references.citation: Development. 2005 Nov;132(21):4869-81
references.pmid: 16207761
references.citation: Philos Trans R Soc Lond B Biol Sci. 2009 Apr 12;364(1519):1021-32
references.pmid: 19064346
references.citation: Development. 2009 May;136(9):1549-57
references.pmid: 19363156
references.citation: J Neurosci. 2009 Apr 15;29(15):4756-67
references.pmid: 19369545
references.citation: Dev Neurobiol. 2012 Mar;72(3):269-81
references.pmid: 22553774
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5842-7
references.pmid: 17389358