14-P019 Netrin1 in forebrain development

MECHANISMS OF DEVELOPMENT

1 2 6 ( 2 0 0 9 ) S 2 3 9 –S 2 4 6

S245

stages and defining the target populations the stromal cells act

serotonergic- and two classes of cholinergic neurons. The intro-

upon.

duction of ID into the ES cell derived neuronal progenitors results

doi:10.1016/j.mod.2009.06.637

in the induction of the right developmental program and suppresses alternative programs by rendering the cell less sensitive to the extrinsic environment. Gene expression profiling shows

14-P019 Netrin1 in forebrain development Janne Hakanen, Se´bastien Duprat, Marjo Salminen University of Helsinki, Helsinki, Finland

that the in vitro generated neurons are similar to their in vivo counterparts and will give us new insights in genes involved in the specification of post-mitotic neurons. doi:10.1016/j.mod.2009.06.639

Netrin1 is a member of a family of secreted molecules implicated in axon guidance, neuronal migration and apoptosis during

14-P021

development of central nervous system (CNS). Netrin1 signals in

The role of gliosis and extracellular matrix proteins in rod pho-

CNS through a group of transmembrane receptors belonging to

toreceptor precursor transplantation in the degenerating retina

the DCC (deleted in colorectal cancer) and C. elegans Unc5-related

A.C. Barber1, J.W.B. Bainbridge1, J.C. Sowden2, R.R. Ali1,

families. Netrin1 mutant mice die usually at birth with several

R.A. Pearson1

CNS defects, but heterozygous mice are normal. We made Netrin1 expression analysis in developing and postnatal mouse brain. Netrin1 was strongly expressed in the proliferative ventricular zone (VZ) in embryonic brain and in the developmentally related ependymal layer of the postnatal brain. Isolated Netrin1 positive

1

2

neurons, astrocytes and oligodendrocytes. Netrin1 expressing cells were also apparent in the rostral migratory stream (RMS), along which newly born neuroblasts migrate from lateral ventricles to the olfactory bulb contributing a constant renewal of the peripheral olfactory system. Netrin1 –/– mice had a smaller olfactory bulbs and immunohistological analysis revealed that Netrin1 expressing cells form a heterogenous subset of precursor cells contributing both neural and glial populations in olfactory bulb. doi:10.1016/j.mod.2009.06.638

Developmental Biology Unit, UCL Institute of Child Health, London,

United Kingdom

neurospheres from VZ/ependymal layer expressed several neural stem cell markers, were able to self-renew and differentiated into

Department of Genetics, UCL Institute of Ophthalmology, London,

United Kingdom

Transplantation of rod photoreceptor precursors leads to their integration in the wildtype retinae but the number of integrated cells is far lower when transplanted into degenerating retinae. Sizable and robust integration into the degenerating retinae must be achieved for photoreceptor transplantation to be considered as a future therapy. It is important to address factors within the host environment that may impede integration and migration of the transplanted cells. Retinal degeneration is often associated with reactive gliosis, a process characterized by the up-regulation of intermediate filament proteins, Muller cell proliferation and gliotic scar formation in the subretinal space. Gliotic scars can act as a reservoir for inhibitory extracellular matrix proteins, including chondroitin sulphate proteoglycans, which have been shown to

14-P020

inhibit axon and neurite growth in the spinal cord and CNS. Enzy-

Intrinsic transcriptional determinants promote efficient genera-

matic digestion using chondroitinase ABC has been shown to

tion of neuronal subtypes from ES cells

improve axonal migration in the spinal cord and cell integration

Lia Panman1, Elisabet Andersson2, Eva Hedlund1, Chris Udhe2,

in injury models of the retina. Here we characterize the progres-

Jamie Mong1, Zhanna Alexsenko2, Rickard Sandberg2,

sion of gliosis and assess its impact on impeding the integration

Johan Ericson2, Thomas Perlmann1

of transplanted rod photoreceptor precursor cells in a number of

1

LICR, Stockholm, Sweden

2

Karolinska institute, Stockholm, Sweden During vertebrate nervous system development distinct clas-

ses of neurons are generated at defined positions within the neural tube in response to several signaling molecules. Ventral neuronal cell fates are specified by Sonic Hedgehog (SHH), which

mouse models of retinal degeneration. Using chondroitinase ABC we observed a significant increase in integration in mouse models of degeneration. This suggests that components of the gliotic scar and extracellular matrix proteins present a barrier to the migration and integration of transplanted precursor cells within the degenerating retina. doi:10.1016/j.mod.2009.06.640

regulates the expression of progenitor specific transcription factors in a concentration dependent manner. The induction of these transcription factors promotes the specification of a particular neuronal cell type, while at the same time alternative cell fates are repressed. Remarkably, during the in vitro differentiation of ventral neurons from mouse embryonic stem cells one specific concentration of SHH results in the generation of several distinct classes of neuronal cell-types at the same time. However,

14-P022 Ethanol-induced DNA damage alters transcript regulation and cell proliferation in neural stem cells by restricting passage through the g1/s checkpoint Steven Hicks1, Frank Middleton1, Michael Miller1,2

by forced expression of ventral progenitor specific intrinsic deter-

1

SUNY Upstate Medical University, Syracuse NY, United States

minants (ID) in ES cell derived neuronal progenitor cell we are

2

Research Service, Veterans Affairs Medical Center, Syracuse NY, United

able to generate homogeneous populations of dopaminergic-,

States