Proper cerebellar development requires expression of β1-integrin in Bergmann glia, but not in granule neurons.
Standard
Proper cerebellar development requires expression of β1-integrin in Bergmann glia, but not in granule neurons. / Frick, Alexandra; Grammel, Daniel; Schmidt, Felix; Pöschl, Julia; Priller, Markus; Pagella, Pierfrancesco; von Bueren, André; André, O; Peraud, Aurelia; Tonn, Jörg-Christian; Rutkowski, Stefan; Rutkowski, Stefan; Kretzschmar, Hans A; Schüller, Ulrich.
In: GLIA, Vol. 60, No. 5, 5, 2012, p. 820-832.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Proper cerebellar development requires expression of β1-integrin in Bergmann glia, but not in granule neurons.
AU - Frick, Alexandra
AU - Grammel, Daniel
AU - Schmidt, Felix
AU - Pöschl, Julia
AU - Priller, Markus
AU - Pagella, Pierfrancesco
AU - von Bueren, André
AU - André, O
AU - Peraud, Aurelia
AU - Tonn, Jörg-Christian
AU - Rutkowski, Stefan
AU - Rutkowski, Stefan
AU - Kretzschmar, Hans A
AU - Schüller, Ulrich
PY - 2012
Y1 - 2012
N2 - Beta1-class integrins play essential roles both in developmental biology as well as in cancer. Particularly, a Nestin-driven deletion of ?1-integrin receptors results in severe abnormalities of brain development including a laminar disorganization of cerebellar granule neurons. However, since Nestin is expressed in all kinds of neural precursors, these data do not allow conclusions to be drawn about the role of Beta1-integrins in distinct neuronal and glial cell types. By generating conditional knockout mice using granule cell-specific Math1-promoter sequences, we show here that the expression of Beta1-integrins in granule neurons is dispensable for the development of the cerebellum. Also, deletion of Beta1-integrin from tumors that arise in a mouse model of granule cell precursor-derived medulloblastoma did not result in a significant survival benefit. Last, expression levels of Beta1-integrin in human medulloblastoma samples did not predict patient's outcome. However, a Beta1-integrin knockout using hGFAP-promoter sequences led to cerebellar hypoplasia, inappropriate positioning of Bergmann glia cells in the molecular layer, undirected outgrowth of radial glia fibers, and granule cell ectopia. We therefore conclude that Beta1-integrin expression in cerebellar granule neurons is not essential during normal development or medulloblastoma formation. In fact, it is the expression of ?1-integrin in glia that is crucial for the proper development of the cerebellar cortex.
AB - Beta1-class integrins play essential roles both in developmental biology as well as in cancer. Particularly, a Nestin-driven deletion of ?1-integrin receptors results in severe abnormalities of brain development including a laminar disorganization of cerebellar granule neurons. However, since Nestin is expressed in all kinds of neural precursors, these data do not allow conclusions to be drawn about the role of Beta1-integrins in distinct neuronal and glial cell types. By generating conditional knockout mice using granule cell-specific Math1-promoter sequences, we show here that the expression of Beta1-integrins in granule neurons is dispensable for the development of the cerebellum. Also, deletion of Beta1-integrin from tumors that arise in a mouse model of granule cell precursor-derived medulloblastoma did not result in a significant survival benefit. Last, expression levels of Beta1-integrin in human medulloblastoma samples did not predict patient's outcome. However, a Beta1-integrin knockout using hGFAP-promoter sequences led to cerebellar hypoplasia, inappropriate positioning of Bergmann glia cells in the molecular layer, undirected outgrowth of radial glia fibers, and granule cell ectopia. We therefore conclude that Beta1-integrin expression in cerebellar granule neurons is not essential during normal development or medulloblastoma formation. In fact, it is the expression of ?1-integrin in glia that is crucial for the proper development of the cerebellar cortex.
KW - Adult
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Adolescent
KW - Young Adult
KW - Child
KW - Child, Preschool
KW - Infant
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - Mice, Transgenic
KW - Antigens, CD29/biosynthesis/genetics
KW - Cerebellum/growth & development/immunology/metabolism
KW - Cytoplasmic Granules/immunology/metabolism
KW - Gene Expression Regulation/immunology
KW - Neuroglia/immunology/metabolism
KW - Neurons/immunology/metabolism
KW - Adult
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Adolescent
KW - Young Adult
KW - Child
KW - Child, Preschool
KW - Infant
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - Mice, Transgenic
KW - Antigens, CD29/biosynthesis/genetics
KW - Cerebellum/growth & development/immunology/metabolism
KW - Cytoplasmic Granules/immunology/metabolism
KW - Gene Expression Regulation/immunology
KW - Neuroglia/immunology/metabolism
KW - Neurons/immunology/metabolism
M3 - SCORING: Journal article
VL - 60
SP - 820
EP - 832
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 5
M1 - 5
ER -
