Cell type specificity and developmental expression of the L2/HNK-1 epitopes in mouse cerebellum

Wernecke, H; Lindner, J.; Schachner, Melitta

doi:10.1016/s0165-5728(85)80012-6

Cited by 59 publications

(31 citation statements)

References 29 publications

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“…Cell adhesion experiments with small cerebellar neurons, 85% of which express the HNK-1 carbohydrate (Wernecke et al, 1985), were performed to investigate whether peptide 5-G2 also interferes with the adhesion of neural cells to laminin. In the presence of peptide 5-G2, cell adhesion was inhibited by 63 ± 3% at a concentration of 83 uM ( Figure 4).…”

Section: Resultsmentioning

confidence: 99%

Characterization of a 21 amino acid peptide sequence of the laminin G2 domain that is involved in HNK-1 carbohydrate binding and cell adhesion

Hall

Vorherr

Schachner³

1995

Glycobiology

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The N-linked HNK-1 carbohydrate expressed by several recognition molecules mediates the adhesion of early postnatal cerebellar neurons to the G2 domain of the terminal globular domain of the laminin al chain (H.Hall et al., submitted). To define this binding site more precisely, G2-derived synthetic peptides were used for binding and competition studies. Peptide 5-G2, comprising the amino add residues 3431-3451 of G2, inhibited the interaction between the HNK-1-carrying glycolipid and laminin in a concentrationdependent and saturable manner. Peptides which overlap only partially with this sequence interfered less. Peptides comprising other amino acid sequences from G2, and peptides derived from Gl and G3 or a scrambled version of peptide 5-G2, did not show significant effects. Direct binding of peptide 5-G2 to the HNK-1 glycolipid was also demonstrated. Furthermore, peptide 5-G2 interfered in a concentration-dependent and saturable manner with the adhesion of early postnatal cerebellar neurons to laminin. These observations indicate that amino acid residues 3431-3451 of the laminin G2 domain are involved in HNK-1 carbohydratemediated cell adhesion.

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Section: Resultsmentioning

confidence: 99%

Characterization of a 21 amino acid peptide sequence of the laminin G2 domain that is involved in HNK-1 carbohydrate binding and cell adhesion

Hall

Vorherr

Schachner³

1995

Glycobiology

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“…The GFP -population included cells with markers of neuronal (HNK-1, polysialated (PSA) NCAM, MAP-2; refs. [13][14][15], oligodendrocyte (O4, NG2; refs. 16,17 ) and astrocyte lineages (GFAP, TAPA-1, CD44; refs.…”

Section: Non-granule Cell Precursors Proliferate In Response To Bfgfmentioning

confidence: 99%

Isolation of neural stem cells from the postnatal cerebellum

et al. 2005

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The cerebellum is critical for motor coordination and cognitive function and is the target of transformation in medulloblastoma, the most common malignant brain tumor in children. Although the development of granule cells, the most abundant neurons in the cerebellum, has been studied in detail, the origins of other cerebellar neurons and glia remain poorly understood. Here we show that the murine postnatal cerebellum contains multipotent neural stem cells (NSCs). These cells can be prospectively isolated based on their expression of the NSC marker prominin-1 (CD133) and their lack of markers of neuronal and glial lineages (lin -). Purified prominin + lin -cells form self-renewing neurospheres and can differentiate into astrocytes, oligodendrocytes and neurons in vitro. Moreover, they can generate each of these lineages after transplantation into the cerebellum. Identification of cerebellar stem cells has important implications for the understanding of cerebellar development and the origins of medulloblastoma.The cerebellum is required for motor coordination and is crucial for cognitive and affective processing 1 . These functions depend on interactions among at least six types of neurons and two types of glia 2 . Disruption of cerebellar structure and function is associated with disorders such as ataxia, autism and schizophrenia 3-5 . In addition, uncontrolled growth of cerebellar precursors results in medulloblastoma 6,7 . Elucidating the mechanisms that control the generation of cerebellar neurons and glia during normal development is critical for understanding the basis of these diseases.The cerebellum differs from most other brain regions in that it contains two distinct germinal layers: the ventricular zone (VZ), which is most active during embryonic development, and the external germinal layer (EGL), which contributes to neurogenesis after birth 2 . There is strong evidence that Purkinje cells, the major output neurons of the cerebellum, originate from the VZ and that granule cells, the most abundant interneurons, arise from the EGL. However, the origin of the other cell types in the cerebellar cortex-including astrocytes, oligodendrocytes and stellate, basket, Lugaro and Golgi interneurons-is much less clear. Tissue grafting and transplantation studies suggest that many of these cells arise from VZ progenitors that migrate into the cerebellar cortex after birth 8,9 . But whether each class of neuron and glial cell comes from a distinct progenitor or whether they all come from a common, multipotent progenitor is not known. Here we purify a population of multipotent neural stem cells from the postnatal cerebellum. We show that this population can undergo self-renewal in culture and can generate neurons, astrocytes and oligodendrocytes both in vitro and after transplantation. Our findings suggest that cerebellar neurons and glia could be generated from a common progenitor. In addition, the approach we have used may be applicable for isolating NSCs from other parts of the nervous system. RESULTS Non-g...

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“…This protocol does not, however, separate proliferating immature GCPs from postmitotic differentiating GCPs. To do this, we used the HNK-1 monoclonal antibody, which has been reported to label cells in the outermost, proliferative zone of the EGL (11).…”

Section: Separation Of Proliferating Gcps From Postmitotic Gcpsmentioning

confidence: 99%

Cerebellar granule cell precursors can differentiate into astroglial cells

Okano-Uchida

Himi

Komiya

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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During CNS development, multipotent neural stem cells give rise first to various kinds of specified precursor cells, which proliferate extensively before terminally differentiating into either neurons or glial cells. It is still not clear, however, whether the specified precursor cells are irreversibly determined to differentiate into their particular cell types. In this study, we show that isolated mouse cerebellar granule cell precursors from the outermost, proliferative zone of the external germinal layer can differentiate into astroglial cells when exposed to sonic hedgehog (Shh) and bone morphogenetic proteins. These induced cells initially expressed both glial fibrillary acidic protein and neuronal markers, but they then lost their neuronal markers and acquired S100-␤, a marker of differentiated astroglial cells. These results indicate that at least some granule cell precursors are not irreversibly committed to neuronal development but can be induced to differentiate into astroglial cells by appropriate extracellular signals.

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Cell type specificity and developmental expression of the L2/HNK-1 epitopes in mouse cerebellum

Cited by 59 publications

References 29 publications

Characterization of a 21 amino acid peptide sequence of the laminin G2 domain that is involved in HNK-1 carbohydrate binding and cell adhesion

Characterization of a 21 amino acid peptide sequence of the laminin G2 domain that is involved in HNK-1 carbohydrate binding and cell adhesion

Isolation of neural stem cells from the postnatal cerebellum

Cerebellar granule cell precursors can differentiate into astroglial cells

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