14-P014 Nephrogenic potential of mouse bone marrow-derived mesenchymal stem cells

MECHANISMS OF DEVELOPMENT

1 2 6 ( 2 0 0 9 ) S 2 3 9 –S 2 4 6

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Wnt/Hedgehog morphogens in retinal stem cell niche, (ii) ana-

the mortality and morbidity caused by kidney failure and the eco-

lysed Wnt signalling activity (target gene expression, transgenic

nomic aspects associated with kidney transplantation or dialysis,

reporter line) following Hedgehog pathway pharmacological

there is a great need for a new effective treatment for patients

interference, or vice versa, and (iii) investigated retinal cell prolif-

with chronic kidney disease to prevent them from development

eration and determination phenotypes following simultaneous

of ESRD. Due to the plasticity and high differentiation potential

inhibition or activation of the two pathways. Altogether, our data

of stem cells, stem cell-based therapies seem to be an attractive

suggest that Wnt and Hedgehog morphogens form opposite gra-

alternative to traditional approaches. In particular, mesenchymal

dients within retinal stem cell niche and that these signalling

stem cells (MSCs) derived from bone marrow, an adult multipo-

pathways antagonize with each other to control retinal stem cell

tent cell population, has attracted considerable attention over

proliferation and multipotence. Interestingly, our retinal gradient

the last few years. MSCs have been described to exert renoprotec-

model is reminiscent to the neural tube patterning model.

tive and regenerative effects in experimental models of kidney

doi:10.1016/j.mod.2009.06.631

injury and even contribute to nephrogenesis. Nevertheless, some reports suggest no direct involvement of MSCs in renal tissue restoration via differentiation, but rather a differentiation independent mechanism of kidney repair. We aim to elucidate

14-P013

differentiation potential of mouse bone marrow-derived mesen-

Implication of XHairy1/2 transcription factors in retinal stem cell

chymal stem cells towards kidney specific cell types and in this

maintenance

way re-evaluate their regenerative capacity. We are currently

Warif El yakoubi, Morgane Locker, Johanna Hamdache,

using an ex vivo kidney culture system, where labelled MSC are

Karine Parain, Massimo Nichane, Eric Bellefroid, Muriel Perron

combined with mouse kidney rudiments, to determine the contri-

Universite´ Paris Sud 11, Orsay, France The successful exploitation of retinal stem cells in cell based therapies primarily requires to unravel intrinsic and extrinsic

bution of mouse MSCs to embryonic kidney development and consequently, their nephrogenic potential. The effect of the MSC on survival and differentiation of the host kidney cells is also being assessed.

molecular cues that control their proliferation and cell lineage determination. In vivo investigations on retinal stem cells are

doi:10.1016/j.mod.2009.06.633

however presently limited by the lack of reliable markers. The ciliary marginal zone (CMZ) of fish and amphibian offers an exceptional model for retinal stem cell marker identification, as stem

14-P015

cells are confined in an identified area, located at its most periph-

The bHLH transcription factor NeuroD1 is a differentiation factor

eral edge. We recently identified two novel markers, XHairy1 and

during the postnatal olfactory bulb neurogenesis

XHairy2 (orthologs of human Hes1 and Hes4, respectively), which

Camille Boutin1, Olaf Hardt2, Nathalie Core1,

are specifically expressed in the stem cell-containing region of

Antoine de Chevigny1, Andreas Bosio2, Harold Cremer1

the Xenopus retina. Our gain of function experiments suggest

1

that both Xhairy1/2 are involved in the maintenance of a cell sub-

CNRS/Universite´ de la Me´diterrane´e, Marseille, France

2

Miltenyi Biotec, Bergisch Gladbach, Germany

population dedicated to generate adult retinal stem cells, by keeping it in an undifferentiated and proliferative state. Our phar-

In postnatal and adult mammals, the subventricular zone

macological data suggest that XHairy1/2 expression patterns are

(SVZ) lining the lateral wall of the lateral ventricle contains stem

independent of Notch signaling but are differentially affected by

cells that generate transit amplifying precursors that, in turn,

Hedgehog and Wnt signaling pathways.

give rise to neuroblasts. These cells migrate along a specific path-

doi:10.1016/j.mod.2009.06.632

way, the rostral migratory stream (RMS) to reach the olfactory bulb (OB) where they differentiate into GABAergic and dopaminergic interneurons. We showed previously that migratory neuro-

14-P014 Nephrogenic potential of mouse bone marrow-derived mesenchymal stem cells Maria Kuzma-Kuzniarska1, David Edgar2, Simon Kenny3, Patricia Murray1 1

School of Biological Sciences, University of Liverpool, Liverpool, United

blasts undergo exclusively glial differentiation when transplanted into non-neurogenic regions in brain repair paradigms. Therefore, we aimed at the identification of factors inducing irreversible neuronal differentiation. For this purpose, defined precursor and neuron populations were isolated from the adult SVZ and OB by microdissection and magnetic cell sorting (MACSaˆ) and their expression profile was investigated using SuperAmpTM and

Kingdom

microarray technology. Differentially expressed genes have been

2

selected for functional analyses. Among them, we found that

School of Biomedical Sciences, University of Liverpool, Liverpool, United

Kingdom

the bHLH transcription factor NeuroD1 is absent from the precur-

3

sors of periglomerular neurons but strongly induced in the

Institute of Child Health, University of Liverpool, Liverpool, United

Kingdom

mature neurons. We used in vivo electroporation of the postnatal forebrain to investigate the function of this gene and show that

End-stage renal disease (ESRD) refers to irreversible renal fail-

overexpression of NeuroD1 alone is sufficient to induce immedi-

ure, often a progression of chronic kidney disease, which requires

ate morphological differentiation and the expression of neuronal

renal replacement therapy to sustain kidney function. Regarding

markers such as NeuN and MAP2 already in the SVZ and RMS.