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Nat14 is a novel essential regulator of neurogenesis by regulating cytoskeletal remodeling

ABSTRACT: Neuronal development involves massive reorganization of cytoskeletal proteins via posttranslational modifications that facilitates morphological remodeling underlying cell-fate changes. Tubulin acetylation has been shown to be essential in several contexts of cellular motility including neuronal migration during cortical development. However, the repertoire of proteins involved in tubulin acetylation remains poorly known. Here, using global gene expression profiles for a range of cell types representing the three embryonic lineages, we identify the acetyltransferase Nat14 as a novel factor specifically induced during cortical development. We find that the loss of Nat14 in neural progenitors blocks neuronal differentiation. Furthermore, such cells retain their progenitor state as reflected by their gene expression signatures and cellular properties. We next show that the cause of these effects are the lack of timely acetylation of tubulin during cortical development with which Nat14 directly physically associates. Cortical cells depleted for Nat14 also fail to migrate towards upper cortical layers that display high levels of acetylated tubulin. In addition, Nat14 was further essential for cellular migration in vitro. Altogether, our study establishes Nat14 as a novel regulator of cortical development by regulating tubulin acetylation dynamics during neurogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE94118 | GEO | 2018/01/01

SECONDARY ACCESSION(S): PRJNA368969

REPOSITORIES: GEO

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