Early Postnatal In Vivo Gliogenesis From Nestin-Lineage Progenitors Requires Cdk5

David Petrik, Sanghee Yun, Sarah E. Latchney, Sohail Kamrudin, Junie A. LeBlanc, James A. Bibb, Amelia J. Eisch

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The early postnatal period is a unique time of brain development, as diminishing amounts of neurogenesis coexist with waves of gliogenesis. Understanding the molecular regulation of early postnatal gliogenesis may provide clues to normal and pathological embryonic brain ontogeny, particularly in regards to the development of astrocytes and oligodendrocytes. Cyclin dependent kinase 5 (Cdk5) contributes to neuronal migration and cell cycle control during embryogenesis, and to the differentiation of neurons and oligodendrocytes during adulthood. However, Cdk5's function in the postnatal period and within discrete progenitor lineages is unknown. Therefore, we selectively removed Cdk5 from nestin-expressing cells and their progeny by giving transgenic mice (nestin-CreERT2/R26R-YFP/CDK5flox/flox [iCdk5] and nestin-CreERT2/R26R-YFP/CDK5wt/wt [WT]) tamoxifen during postnatal (P) days P2-P 4 or P7-P 9, and quantified and phenotyped recombined (YFP+) cells at P14 and P21. When Cdk5 gene deletion was induced in nestin-expressing cells and their progeny during the wave of cortical and hippocampal gliogenesis (P2-P4), significantly fewer YFP+ cells were evident in the cortex, corpus callosum, and hippocampus. Phenotypic analysis revealed the cortical decrease was due to fewer YFP+ astrocytes and oligodendrocytes, with a slightly earlier influence seen in oligodendrocytes vs. astrocytes. This effect on cortical gliogenesis was accompanied by a decrease in YFP+ proliferative cells, but not increased cell death. The role of Cdk5 in gliogenesis appeared specific to the early postnatal period, as induction of recombination at a later postnatal period (P7-P9) resulted in no change YFP+ cell number in the cortex or hippocampus. Thus, glial cells that originate from nestin-expressing cells and their progeny require Cdk5 for proper development during the early postnatal period.

Original languageEnglish (US)
Article numbere72819
JournalPLoS One
Volume8
Issue number8
DOIs
StatePublished - Aug 26 2013

Fingerprint

Cyclin-Dependent Kinase 5
Nestin
cyclin-dependent kinase
postpartum period
Oligodendroglia
astrocytes
Astrocytes
cells
Brain
hippocampus
Hippocampus
cortex
Cell death
Tamoxifen
Corpus Callosum
brain
tamoxifen
Neurogenesis
Gene Deletion
Neurons

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Early Postnatal In Vivo Gliogenesis From Nestin-Lineage Progenitors Requires Cdk5. / Petrik, David; Yun, Sanghee; Latchney, Sarah E.; Kamrudin, Sohail; LeBlanc, Junie A.; Bibb, James A.; Eisch, Amelia J.

In: PLoS One, Vol. 8, No. 8, e72819, 26.08.2013.

Research output: Contribution to journalArticle

Petrik, David ; Yun, Sanghee ; Latchney, Sarah E. ; Kamrudin, Sohail ; LeBlanc, Junie A. ; Bibb, James A. ; Eisch, Amelia J. / Early Postnatal In Vivo Gliogenesis From Nestin-Lineage Progenitors Requires Cdk5. In: PLoS One. 2013 ; Vol. 8, No. 8.
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