Dataset Information

Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord.

ABSTRACT: Glia constitute the majority of cells in the mammalian central nervous system and are crucial for neurological function. However, there is an incomplete understanding of the molecular control of glial cell development. We find that the transcription factor Ascl1 (Mash1), which is best known for its role in neurogenesis, also functions in both astrocyte and oligodendrocyte lineages arising in the mouse spinal cord at late embryonic stages. Clonal fate mapping in vivo reveals heterogeneity in Ascl1-expressing glial progenitors and shows that Ascl1 defines cells that are restricted to either gray matter (GM) or white matter (WM) as astrocytes or oligodendrocytes. Conditional deletion of Ascl1 post-neurogenesis shows that Ascl1 is required during oligodendrogenesis for generating the correct numbers of WM but not GM oligodendrocyte precursor cells, whereas during astrocytogenesis Ascl1 functions in balancing the number of dorsal GM protoplasmic astrocytes with dorsal WM fibrous astrocytes. Thus, in addition to its function in neurogenesis, Ascl1 marks glial progenitors and controls the number and distribution of astrocytes and oligodendrocytes in the GM and WM of the spinal cord.

SUBMITTER: Vue TY

PROVIDER: S-EPMC4197573 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord.

Vue Tou Yia TY Kim Euiseok J EJ Parras Carlos M CM Guillemot Francois F Johnson Jane E JE

Development (Cambridge, England) 20140905 19

Glia constitute the majority of cells in the mammalian central nervous system and are crucial for neurological function. However, there is an incomplete understanding of the molecular control of glial cell development. We find that the transcription factor Ascl1 (Mash1), which is best known for its role in neurogenesis, also functions in both astrocyte and oligodendrocyte lineages arising in the mouse spinal cord at late embryonic stages. Clonal fate mapping in vivo reveals heterogeneity in Ascl ...[more]

PMID: 25249462

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Project description:In multiple sclerosis (MS), upper cervical cord gray matter (GM) atrophy correlates more strongly with disability than does brain or cord white matter (WM) atrophy. The corresponding relationships in the thoracic cord are unknown owing to technical difficulties in assessing GM and WM compartments by conventional magnetic resonance imaging techniques.To investigate the associations between MS disability and disease type with lower thoracic cord GM and WM areas using phase-sensitive inversion recovery magnetic resonance imaging at 3 T, as well as to compare these relationships with those obtained at upper cervical levels.Between July 2013 and March 2014, a total of 142 patients with MS (aged 25-75 years; 86 women) and 20 healthy control individuals were included in this cross-sectional observational study conducted at an academic university hospital.Total cord areas (TCAs), GM areas, and WM areas at the disc levels C2/C3, C3/C4, T8/9, and T9/10. Area differences between groups were assessed, with age and sex as covariates.Patients with relapsing MS (RMS) had smaller thoracic cord GM areas than did age- and sex-matched control individuals (mean differences [coefficient of variation (COV)]: 0.98 mm2 [9.2%]; P?=?.003 at T8/T9 and 0.93 mm2 [8.0%]; P?=?.01 at T9/T10); however, there were no significant differences in either the WM area or TCA. Patients with progressive MS showed smaller GM areas (mean differences [COV]: 1.02 mm2 [10.6%]; P?<?.001 at T8/T9 and 1.37 mm2 [13.2%]; P?<?.001 at T9/T10) and TCAs (mean differences [COV]: 3.66 mm2 [9.0%]; P?<?.001 at T8/T9 and 3.04 mm2 [7.2%]; P?=?.004 at T9/T10) compared with patients with RMS. All measurements (GM, WM, and TCA) were inversely correlated with Expanded Disability Status Scale score. Thoracic cord GM areas were correlated with lower limb function. In multivariable models (which also included cord WM areas and T2 lesion number, brain WM volumes, brain T1 and fluid-attenuated inversion recovery lesion loads, age, sex, and disease duration), cervical cord GM areas had the strongest correlation with Expanded Disability Status Scale score followed by thoracic cord GM area and brain GM volume.Thoracic cord GM atrophy can be detected in vivo in the absence of WM atrophy in RMS. This atrophy is more pronounced in progressive MS than RMS and correlates with disability and lower limb function. Our results indicate that remarkable cord GM atrophy is present at multiple cervical and lower thoracic levels and, therefore, may reflect widespread cord GM degeneration.

Dataset Information

Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord.

Publications

Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord.

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