Spatially distinct functions of PAX6 and NKX2.2 during gliogenesis in the ventral spinal cord

Genethliou, Nicholas; Panayiotou, Elena; Panayi, Helen; Orford, Michael; Mean, Richard; Lapathitis, George; Malas, Stavros

doi:10.1016/j.bbrc.2009.02.134

Cited by 12 publications

(9 citation statements)

References 26 publications

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“…8B). The cross-repressive interactions of Pax6 and Nkx2.2 (Briscoe et al, 1999;Ericson et al, 1997) (Genethliou et al, 2009;Sugimori et al, 2007), where we found a reduced Tnc expression. The domain shift is most probably due to modified Shh signalling.…”

Section: Research Articlesupporting

confidence: 49%

“…Sulf1 is a downstream target of Nkx2.2 (Genethliou et al, 2009) and is expressed in the developing ventral spinal cord during the neuronto-glia switch (Ratzka et al, 2010). Furthermore, Sulf1 influences both FGF and bone morphogenetic protein (BMP) signalling (Lamanna et al, 2008;Otsuki et al, 2010).…”

Section: Tnc-deficiency Leads To Alterations In Growth Factor Responsmentioning

confidence: 99%

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The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification

et al. 2011

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SUMMARYThe generation of astrocytes during the development of the mammalian spinal cord is poorly understood. Here, we demonstrate for the first time that the extracellular matrix glycoprotein tenascin C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that tenascin C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of tenascin C leads to a sustained generation and delayed migration of Fgfr3-expressing immature astrocytes in vivo. Consistent with an increased generation of astroglial cells, we documented an increased number of GFAP-positive astrocytes at later stages. Mechanistically, we could demonstrate an upregulation and domain shift of the patterning genes Nkx6.1 and Nkx2.2 in vivo. In addition, sulfatase 1, a known downstream target of Nkx2.2 in the ventral spinal cord, was also upregulated. Sulfatase 1 regulates growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this function, we observed changes in both FGF2 and EGF responsiveness of spinal cord neural precursor cells. Taken together, our data implicate Tnc in the regulation of proliferation and lineage progression of astroglial progenitors in specific domains of the developing spinal cord.

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Section: Research Articlesupporting

confidence: 49%

Section: Tnc-deficiency Leads To Alterations In Growth Factor Responsmentioning

confidence: 99%

The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification

et al. 2011

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“…Amphioxus Ptc, Smo , and Sufu also appear in the neural ectoderm, the notochord, the gill slits, the gut, and the somites. Thus the expression patterns of amphioxus Hh, Ptc, Smo, Sufu , and Gli are similar to those of the vertebrates (Bumcrot and McMahon 1995; Liem et al 2000; Zhang et al 2000; Ito et al 2001; Christ et al 2004; Cairns et al 2008; Genethliou et al 2009; Szabo et al 2009).…”

Section: Discussionmentioning

confidence: 52%

Ptc, Smo, Sufu, and the Hedgehog signaling pathway in amphioxus

Lin¹,

Cai²,

Huang³

et al. 2009

Evolution and Development

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The Hedgehog (Hh) signaling pathway regulates many developmental processes both in vertebrates and in invertebrates. However, little is known about this pathway in the cephalochordate amphioxus. In this paper, we focus on the Ptc, Smo, and Sufu homologs in amphioxus, which are the key members of the Hh signaling pathway. Their genomic structures show their comparability with homologs in vertebrates. In situ hybridization reveals that amphioxus Ptc, Smo, and Sufu have similar expression patterns in embryogenesis. They are expressed in the neural plate at early neurula stage, and then down-regulated in dorsal neural ectoderm. During development, their transcripts appear and persist in the notochord, the wall of the head cavity, the epithelium of the pharynx, and the gut. The data show that the expression patterns of these three genes are overlapping with Hh and Gli during the embryonic development in amphioxus. Moreover, injection of amphioxus Hh RNA into zebrafish-fertilized eggs can expand the expression domains of Ptc1 and Nk2.2a, the target genes of the Hh signaling pathway, which is similar to the injection of zebrafish Sonic hh a (zShha) and Sonic hh b (zShhb). Our results suggest that amphioxus may possess a conserved and functional Hh signaling pathway similar to that of vertebrates.

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“…The failure to stabilize high GliR levels can therefore explain the progressive dorsal expansion of Nkx2.2 in Pax6 mutants (Novitch et al, 2001), as well as the restored induction of FP differentiation observed in Pax6;Gli2 compound mutants. Loss of Pax6 function influences not only FP induction and the position of the p3/pMN boundary, but also results in more general patterning defects over time (Genethliou et al, 2009). Moreover, overexpression of Pax6 in the intermediate neural tube results in reduced Nkx6.1 and ventral expansion of Dbx2 expression.…”

Section: Pax6 Provides Responding Cells With Intrinsic Resistance To mentioning

confidence: 99%

A homeodomain feedback circuit underlies step-function interpretation of a Shh morphogen gradient during ventral neural patterning

et al. 2010

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SUMMARYThe deployment of morphogen gradients is a core strategy to establish cell diversity in developing tissues, but little is known about how small differences in the concentration of extracellular signals are translated into robust patterning output in responding cells. We have examined the activity of homeodomain proteins, which are presumed to operate downstream of graded Shh signaling in neural patterning, and describe a feedback circuit between the Shh pathway and homeodomain transcription factors that establishes non-graded regulation of Shh signaling activity. Nkx2 proteins intrinsically strengthen Shh responses in a feed-forward amplification and are required for ventral floor plate and p3 progenitor fates. Conversely, Pax6 has an opposing function to antagonize Shh signaling, which provides intrinsic resistance to Shh responses and is important to constrain the inductive capacity of the Shh gradient over time. Our data further suggest that patterning of floor plate cells and p3 progenitors is gated by a temporal switch in neuronal potential, rather than by different Shh concentrations. These data establish that dynamic, non-graded changes in responding cells are essential for Shh morphogen interpretation, and provide a rationale to explain mechanistically the phenomenon of cellular memory of morphogen exposure.

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Spatially distinct functions of PAX6 and NKX2.2 during gliogenesis in the ventral spinal cord

Cited by 12 publications

References 26 publications

The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification

The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification

Ptc, Smo, Sufu, and the Hedgehog signaling pathway in amphioxus

A homeodomain feedback circuit underlies step-function interpretation of a Shh morphogen gradient during ventral neural patterning

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