Verslag – Rapport – Bericht – Report - GSKE - FMRE

More documents

Recommendations

Info

Prof. dr. Christophe Ampe Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University. A. Baertsoenkaai 3 9000 Gent Tel: 09/264 9336 FAX: 09/264 9488 christophe.ampe@ugent.be 10 Verslag – Rapport – Report 2012
ß-actin in neural crest cell migration and brain development Background The actin cytoskeleton is the driving force behind cell motility processes in health and diseases (Lambrechts et al., 2004). One main process during development that requires cell motility, is neural crest cell migration and subsequent neurogenesis (Kawauchi en Hoshino 2008). Indeed actin polymerization forms the propulsive force for cell migration, for neurite outgrowth and is an essential mediator in growth cone steering. In neuronal cells two actin isoforms are present: b- and g- cytoplasmic actin (Tondeleir et al., 2009). It was long time accepted these isoforms were functionally redundant because they only differ in four amino acids. Recent studies employing mice show, however, these isoforms are not redundant but their differential roles are only slowly being unraveled. g-actin knock-out (KO) mice are viable but show progressive hearing loss during adulthood, despite compensatory up-regulation of b-actin (Belyantseva et al., 2009) whereas b-actin KOs are embryonically lethal beyond E10.5 (Schmerling et al., 2005) despite up regulation of g-actin and ectopic expression of a-smooth muscle actin at these stages (Tondeleir et al., 2012). Clearly the increased expression of other actin isoforms fails to rescue the lethal phenotype and does not compensate for lack of b-actin. Additionally expressing g-actin from the b-actin locus does not rescue the lethal phenotype although occasionally embryos survive until E13.5-14.5 suggesting partial rescue (Lambrechts et al., unpublished). Various studies on conditional b-actin knock-outs (Actb -/- ) exist. Surprisingly, depletion of b-actin at late stages of motor neuron development or brain development yield only mild defects (Cheever et al., 2011; Cheever et al., 2012). Viable central nervous system Actb -/- mice display restricted histological abnormalities in the hippocampus and cerebellum. These morphology defects correlated with hyperactivity and cognitive impairments (Cheever et al., 2012). These restricted effects in vivo at late stages of brain development strongly contrast with the dramatic effects on NCC migration presented below. b-actin is the form traditionally associated with cell migration but more and more a role for transcriptional regulation becomes evident (Visa and Percipalle, 2010). Primary embryonic fibroblasts (MEFs) isolated from the knock-out mouse have increased expression of g- and a-smooth muscle actin and (re)differentiate to a myofibroblast-like phenotype. These cells display strongly impaired cell migration and increased adhesion. In addition we observed that the Rho – Rho-kinase (ROCK) pathway is over-activated and the MEFs have sustained transforming growth factor b (TGF-b) activity. Inhibiting ROCK or myosin contractility restores cell migration, strongly indicating that altered signaling is generating the impaired migration, rather than lack of actin polymerization capacity (Tondeleir et al. 2012). Collectively, our results point to an important role of actin in cell and organ differentiation via its essential nuclear function (Tondeleir et al. 2012, Tondeleir et al., submitted A) and not via its traditional role as engine for cell motility. Also the result presented in the 2012 report on neural crest cells point in this direction (Tondelier et al., submitted B). Verslag – Rapport – Report 2012 11
Page 1 and 2: Verslag - Rapport - Bericht - Repor
Page 3 and 4: Fondation Médicale Reine Elisabeth
Page 5 and 6: Onderzoeksprogramma’s gefinancier
Page 7 and 8: Progress reports of the university
Page 9: Progress report of the research gro
Page 13 and 14: In addition whole mount in situ hyb
Page 15 and 16: In summary we show an essential rol
Page 17 and 18: Progress report of the research gro
Page 19 and 20: mRNA metabolism at synapses and spi
Page 21 and 22: eIF4E upon DHPG stimulation, but Ra
Page 23 and 24: REFERENCES - Bagni, C., Tassone, F.
Page 27 and 28: Role of DMRT transcription factors
Page 29 and 30: References - Borello U, Pierani A (
Page 33 and 34: Molecular Genetics and Functional G
Page 35 and 36: Granulin (GRN) Loss-of-function mut
Page 37 and 38: Publications Acknowledging G.S.K.E.
Page 39 and 40: - van der Zee J.: “A European con
Page 43 and 44: Developmental origin of multiple de
Page 45 and 46: additional experiments, which meanw
Page 47 and 48: using Sip1-deficient, Cre-activated
Page 49 and 50: Hirschsprung disease-mental retarda
Page 51 and 52: Verslag - Rapport - Report 2012 51
Page 55 and 56: Characterization of Human Sleep/Wak
Page 57 and 58: delivery. These detected sounds wer
Page 61 and 62:
Unravelling the roles of lysine ace
Page 63 and 64:
candidate-based approach with a pro
Page 65 and 66:
Bibliography - Akella, J.S., Wloga,
Page 67 and 68:
Verslag - Rapport - Report 2012 67
Page 69 and 70:
Progress report of the research gro
Page 71 and 72:
Roles of Specific Neuronal Populati
Page 73 and 74:
clamp recording and optogenetics ha
Page 75 and 76:
2 Regulation of striatal neurons ex
Page 77 and 78:
patch clamp recordings, presynaptic
Page 79 and 80:
- Schmidt H., Brachtendorf S., Aren
Page 81 and 82:
Page 83 and 84:
Unveiling the role of the cystine/g
Page 85 and 86:
We hypothesise that upregulation of
Page 87 and 88:
To support the view that the observ
Page 89 and 90:
- 5 Development of new x research t
Page 91 and 92:
Page 93 and 94:
Page 95 and 96:
Charcot-Marie-Tooth neuropathies; f
Page 97 and 98:
Reference List 1. Rotthier,A., Baet
Page 99 and 100:
Slide presentations selected at int
Page 101 and 102:
Page 103 and 104:
Celsr genes in brain development an
Page 105 and 106:
cells sometimes pointed to, or oppo
Page 107 and 108:
Page 109 and 110:
Page 111 and 112:
Study of the role of the NF-kB regu
Page 113 and 114:
Since A20 is a key negative regulat
Page 115 and 116:
References - De Jager, P.L. et al.
Page 117 and 118:
Page 119 and 120:
Page 121 and 122:
From stem cells to cortical network
Page 123 and 124:
We have thus generated a unique exp
Page 125 and 126:
Publications resulting from work pe
show all

Verslag – Rapport – Bericht – Report - GSKE - FMRE

Create successful ePaper yourself

Delete template?

Save as template?