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Health Research (MOP93803).

doi:10.1016/j.ijdevneu.2012.03.297

60 P.P. Kale, V. Addepalli / Int. J. D

etinoic acid maintains olfactory progenitor cells during neu-ogenesis and regeneration

arie Paschaki 1, Yuko Muta 1, Yoko Matsuoka 1, Siu-Shan Mak 1,aura Cammas 2, Pascal Dolle 2, Raj Ladher 1,∗

RIKEN CDB, JapanIGBMC, France-mail address: raj-ladher@cdb.riken.jp (R. Ladher).

In order to fulfil its chemosensory role, olfactory neurons mustxtend their dendrites into the external environment. This contactakes them prone to damage. However, function is maintained

hroughout life due to a series of progenitors present in thelfactory epithelium that are capable of replacing and replenishingamaged olfactory neurons. This makes the olfactory epitheliumne of the few regenerating neuronal populations in adult mam-als. However the mechanisms that control regeneration are notell characterized. We show that retinoic acid (RA) promotes Pax6ositive olfactory basal cells, and prevents their progression intoommitted neuronal precursors. RA depletion results in a failuref progenitor maintenance and consequently, due to progenitorepletion, differentiation is not sustained. Furthermore, the regen-rative capacity of olfactory epithelium from mice mutant foretinaldehyde dehydrogenase 3 (raldh3) is impaired. Our data sug-est a mechanism by which local modulation of RA may triggerlfactory repair and renewal in adults.

oi:10.1016/j.ijdevneu.2012.03.294

Dlx2-negative GABAergic population in the diencephalonives rise to the subcortical visual shell and requires Sox14xpression for its function in entrainment of the circadianhythm to light

lessio Delogu 1,∗, Katherine Sellers 1, David Sugden 2, Johnubenstein 3, Thomas Jessell 4, Andrew Lumsden 1

MRC Centre for Developmental Neurobiology, UKDivisions of Women’s Health, School of Medicine, King’s College Lon-on, UKNina Ireland Laboratory of Developmental Neurobiology, Depart-ent of Psychiatry, University of California, San Francisco, CA 94143,SADept of Biochemistry and Molecular Biophysics, Howard Hughesedical Institute, Kavli Institute for Brain Science, Columbia Univer-

ity, New York, NY 10032, USA

A universal characteristic of all complex living organisms is thebility to correlate behaviours and their underlying physiologicalrocesses to environmental variables that cycle with an approxi-ate 24-h period.The hypothalamic suprachiasmatic nucleus (SCN) possesses the

ntrinsic oscillating properties that constitute the biological clocknd light is the major variable in entrainment of the circadianhythm. Intrinsically photosensitive retinal ganglion cells (ipRGCs)onvey information on ambient light intensity directly to the SCNnd to neurons of the subcortical visual shell (SVS) that are locatedn the diencephalon.

The SVS is made up of several interconnected nuclei, the mostrominent of which are: the ventral lateral geniculate (vLGN), the

ntergeniculate leaflet (IGL), the nucleus posterior limitans (PLi)nd the olivary pretectal nucleus (OPN). The SVS mediates light-ependent physiological responses such as the pupillary light reflex

PLR). Some evidence also suggests that the SVS could modulatentrainment of the biological clock at the SCN.

uroscience 30 (2012) 640–671

We describe expression of the transcription factor Sox14 as acommon feature of all SVS nuclei. Using a Sox14gfp reporter mouse,we find that IGL and PLi share a common origin in a narrow stripeof rostral thalamic progenitors specified by the organizer activity ofthe zona limitans intrathalamica (ZLI). We describe a novel role forthe transcription factors Dlx1 and Dlx2 to promote vLGN differenti-ation at the expenses of IGL development. Conversely, we find thatSox14 is required for the correct morphogenesis of the IGL/vLGNcomplex. Furthermore, we characterize the behavioural responsesof Sox14-deficient mice to light changes and find that these animalsare unable to entrain their circadian rhythm to light.

In summary, we present novel experimental evidence on themolecular and developmental steps that underlie formation ofthe SVS during embryogenesis and identify Sox14 as a key playerfor both its development and its function in modulating light-dependent entrainment of the circadian rhythm.

doi:10.1016/j.ijdevneu.2012.03.295

Transgenic zebrafish models for studies of dopamine neurondevelopment, loss and regeneration

Yanwei Xi, Rafael Godoy, Sandra Noble, Man Yu, Marc Ekker ∗

Department of Biology, University of Ottawa, Ottawa, ON, Canada

Zebrafish are increasingly used to study dopamine (DA) neu-ron development and death as well as for the functional analysisof genes associated with familial early onset Parkinson’s disease.We have previously shown that loss of zebrafish pink1 functionleads to impaired patterning of DA neuron and altered movementand escape response in zebrafish larvae. We have also shown thatfunction of the two zebrafish parl genes is necessary for properDA neuron development and for survival. Rescue experiments sug-gested that a common pathway for parl, pink1 and parkin also existsin vertebrates. To facilitate studies of DA neuron development andloss, we have produced lines of transgenic zebrafish, in which trans-genes are inserted in frame within the first exon of the dopaminetransporter (dat) gene, in order to target their expression to DA neu-rons. In transgenic fish carrying an eGFP reporter, Tg(dat:EGFP),DA neurons are labeled, including those in ventral diencephalon(vDC) clusters, amacrine cells in the retina, in the olfactory bulb,in the pretectum, and in the caudal hypothalamus. In the vDC, DAneurons of groups 2–6 are correctly labeled with GFP, based on co-localization analyses. MPTP induced a significant but modest lossof DA neurons in the vDC (groups 2–6) of Tg(dat:EGFP) larvae. Weperformed unilateral laser ablation in the vDC of Tg(dat:EGFP) lar-vae and observed a partial replacement of DA neurons in the vDC(groups 2–6). We produced a similar transgene construct in whichthe nitroreductase gene is expressed in DA neurons, allowing selec-tive ablation of DA neurons with the pro-drug metronidazole. Thesetransgenic lines are useful for the study of DA neuron development,in models of DA neuron loss/regeneration and in chemical screensfor compounds that influence DA neuron survival.

Acknowledgment: Supported by the Canadian Institutes of