Dataset Information

Control of astrocyte progenitor specification, migration and maturation by Nkx6.1 homeodomain transcription factor.

ABSTRACT: Although astrocytes are the most abundant cell type in the central nervous system (CNS), little is known about their molecular specification and differentiation. It has previously been reported that transcription factor Nkx6.1 is expressed in neuroepithelial cells that give rise to astrocyte precursors in the ventral spinal cord. In the present study, we systematically investigated the function of Nkx6.1 in astrocyte development using both conventional and conditional Nkx6.1 mutant mice. At early postnatal stages, Nkx6.1 was expressed in a subpopulation of astrocytes in the ventral spinal cord. In the conventional Nkx6.1KO spinal cord, the initial specification of astrocyte progenitors was affected by the mutation, and subsequent migration and differentiation were disrupted in newborn mice. In addition, the development of VA2 subtype astrocytes was also inhibited in the white matter. Further studies with Nkx6.1 conditional mutants revealed significantly delayed differentiation and disorganized arrangement of fibrous astrocytes in the ventral white matter. Together, our studies indicate that Nkx6.1 plays a vital role in astrocyte specification and differentiation in the ventral spinal cord.

SUBMITTER: Zhao X

PROVIDER: S-EPMC4186865 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Control of astrocyte progenitor specification, migration and maturation by Nkx6.1 homeodomain transcription factor.

Zhao Xiaofeng X Chen Yidan Y Zhu Qiang Q Huang Hao H Teng Peng P Zheng Kang K Hu Xuemei X Xie Binghua B Zhang Zunyi Z Sander Maike M Qiu Mengsheng M

PloS one 20141006 10

Although astrocytes are the most abundant cell type in the central nervous system (CNS), little is known about their molecular specification and differentiation. It has previously been reported that transcription factor Nkx6.1 is expressed in neuroepithelial cells that give rise to astrocyte precursors in the ventral spinal cord. In the present study, we systematically investigated the function of Nkx6.1 in astrocyte development using both conventional and conditional Nkx6.1 mutant mice. At earl ...[more]

PMID: 25285789

Similar Datasets

Project description:Intestinal hormones are key regulators of digestion and energy homeostasis secreted by rare enteroendocrine cells. These cells produce over ten different hormones including GLP-1 and GIP peptides known to promote insulin secretion. To date, the molecular mechanisms controlling the specification of the various enteroendocrine subtypes from multipotent Neurog3(+) endocrine progenitor cells, as well as their number, remain largely unknown. In contrast, in the embryonic pancreas, the opposite activities of Arx and Pax4 homeodomain transcription factors promote islet progenitor cells towards the different endocrine cell fates. In this study, we thus investigated the role of Arx and Pax4 in enteroendocrine subtype specification. The small intestine and colon of Arx- and Pax4-deficient mice were analyzed using histological, molecular, and lineage tracing approaches. We show that Arx is expressed in endocrine progenitors (Neurog3(+)) and in early differentiating (ChromograninA(-)) GLP-1-, GIP-, CCK-, Sct- Gastrin- and Ghrelin-producing cells. We noted a dramatic reduction or a complete loss of all these enteroendocrine cell types in Arx mutants. Serotonin- and Somatostatin-secreting cells do not express Arx and, accordingly, the differentiation of Serotonin cells was not affected in Arx mutants. However, the number of Somatostatin-expressing D-cells is increased as Arx-deficient progenitor cells are redirected to the D-cell lineage. In Pax4-deficient mice, the differentiation of Serotonin and Somatostatin cells is impaired, as well as of GIP and Gastrin cells. In contrast, the number of GLP-1 producing L-cells is increased concomitantly with an upregulation of Arx. Thus, while Arx and Pax4 are necessary for the development of L- and D-cells respectively, they conversely restrict D- and L-cells fates suggesting antagonistic functions in D/L cell allocation. In conclusion, these finding demonstrate that, downstream of Neurog3, the specification of a subset of enteroendocrine subtypes relies on both Arx and Pax4, while others depend only on Arx or Pax4.

Dataset Information

Control of astrocyte progenitor specification, migration and maturation by Nkx6.1 homeodomain transcription factor.

Publications

Control of astrocyte progenitor specification, migration and maturation by Nkx6.1 homeodomain transcription factor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets