SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

Genethliou, Nicholas; Panayiotou, Elena; Panayi, Helen; Orford, Michael; Mean, Richard; Lapathitis, George; Gill, Herman; Raoof, Sahir; Gasperi, Rita De; Elder, Gregory A.; Kessaris, Nicoletta; Richardson, William D.; Malas, Stavros

doi:10.1016/j.bbrc.2009.08.154

Cited by 19 publications

(22 citation statements)

References 36 publications

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“…Indeed, Notch signaling controls the number of progenitors entering retinal differentiation: loss of Notch function forestalls retinal neurogenesis (Jadhav et al, 2006), whereas abnormal Notch receptor activation transiently increases retinal proliferation and differentiation (Esteve et al, 2011). Notably, Meis1 action on the Notch pathway and on microphthalmia-related genes could be linked since Sox1, Sox2 and Notch signaling have been shown to regulate each other's activity in various contexts (Genethliou et al, 2009;Kan et al, 2004;Neves et al, 2011). Most notably, Sox2 regulates the Notch signaling pathway in retinal progenitor cells in a concentration-dependent manner, so that the levels of Sox2 directly correlate with the levels of Notch1 (Taranova et al, 2006), a correlation that we have also observed between Meis1 levels and Hes5 expression.…”

Section: Discussionmentioning

confidence: 99%

Meis1 coordinates a network of genes implicated in eye development and microphthalmia

et al. 2015

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Microphthalmos is a rare congenital anomaly characterized by reduced eye size and visual deficits of variable degree. Sporadic and hereditary microphthalmos have been associated with heterozygous mutations in genes fundamental for eye development. Yet, many cases are idiopathic or await the identification of molecular causes. Here we show that haploinsufficiency of Meis1, which encodes a transcription factor with evolutionarily conserved expression in the embryonic trunk, brain and sensory organs, including the eye, causes microphthalmic traits and visual impairment in adult mice. By combining analysis of Meis1 loss-offunction and conditional Meis1 functional rescue with ChIP-seq and RNA-seq approaches we show that, in contrast to its preferential association with Hox-Pbx BSs in the trunk, Meis1 binds to Hox/Pbxindependent sites during optic cup development. In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway. In addition, Meis1 is required for eye patterning by controlling a set of eye territory-specific transcription factors, so that in Meis1 −/− embryos boundaries among the different eye territories are shifted or blurred. We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations.

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Section: Discussionmentioning

confidence: 99%

Meis1 coordinates a network of genes implicated in eye development and microphthalmia

et al. 2015

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“…In ESCs, NOTCH coordinates the response to neural inductive cues such as FGF, protects the cells against non-neural fates and stimulates proliferation of neural precursors in a cyclin D-dependent manner (Das et al, 2010;Lowell et al, 2006). In addition, in vivo studies have shown that Sox1 expression in the spinal cord depends on NOTCH signalling (Genethliou et al, 2009). Direct induction of Sox1 could similarly be involved in the premature Sox1 expression induced by NOTCH activity in N1ICD epi embryos.…”

Section: Discussionmentioning

confidence: 99%

NOTCH activation interferes with cell fate specification in the gastrulating mouse embryo

et al. 2015

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NOTCH signalling is an evolutionarily conserved pathway involved in intercellular communication essential for cell fate choices during development. Although dispensable for early aspects of mouse development, canonical RBPJ-dependent NOTCH signalling has been shown to influence lineage commitment during embryonic stem cell (ESC) differentiation. NOTCH activation in ESCs promotes the acquisition of a neural fate, whereas its suppression favours their differentiation into cardiomyocytes. This suggests that NOTCH signalling is implicated in the acquisition of distinct embryonic fates at early stages of mammalian development. In order to investigate in vivo such a role for NOTCH signalling in shaping cell fate specification, we use genetic approaches to constitutively activate the NOTCH pathway in the mouse embryo. Early embryonic development, including the establishment of anterior-posterior polarity, is not perturbed by forced NOTCH activation. By contrast, widespread NOTCH activity in the epiblast triggers dramatic gastrulation defects. These are fully rescued in a RBPJ-deficient background. Epiblast-specific NOTCH activation induces acquisition of neurectoderm identity and disrupts the formation of specific mesodermal precursors including the derivatives of the anterior primitive streak, the mouse organiser. In addition, we show that forced NOTCH activation results in misregulation of NODAL signalling, a major determinant of early embryonic patterning. Our study reveals a previously unidentified role for canonical NOTCH signalling during mammalian gastrulation. It also exemplifies how in vivo studies can shed light on the mechanisms underlying cell fate specification during in vitro directed differentiation.

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“…In the developing spinal cord at embryonic day 9.5 (E9.5), Sox1 is expressed only in ventricular zone (VZ) progenitors and not differentiated cells (Pevny et al, 1998;Genethliou et al, 2009). However, from late E10.5, in addition to the VZ expression, we detected Sox1 expression in a small group of differentiated cells migrating close to the p3 domain ( Fig.…”

Section: Sox1 Is Expressed In a Subset Of Interneurons In The Ventralmentioning

confidence: 99%

“…To test whether the V2c IN fate is also attained in postmitotic progenitors, we analyzed V2c IN fate in Pax6 Sey/Sey in which Sox1 expression is lost only in VZ progenitors but not in postmitotic progenitors (Genethliou et al, 2009). To achieve this, we monitored GFP expression in Pax6…”

Section: V2c Ins Are Specified In Postmitotic Progenitorsmentioning

confidence: 99%

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Sox1 Is Required for the Specification of a Novel p2-Derived Interneuron Subtype in the Mouse Ventral Spinal Cord

Panayi¹,

Panayiotou²,

Orford³

et al. 2010

J. Neurosci.

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During mouse development, the ventral spinal cord becomes organized into five progenitor domains that express different combinations of transcription factors and generate different subsets of neurons and glia. One of these domains, known as the p2 domain, generates two subtypes of interneurons, V2a and V2b. Here we have used genetic fate mapping and loss-of-function analysis to show that the transcription factor Sox1 is expressed in, and is required for, a third type of p2-derived interneuron, which we named V2c. These are close relatives of V2b interneurons, and, in the absence of Sox1, they switch to the V2b fate. In addition, we show that late-born V2a and V2b interneurons are heterogeneous, and subsets of these cells express the transcription factor Pax6. Our data demonstrate that interneuron diversification in the p2 domain is more complex than previously thought and directly implicate Sox1 in this process.

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SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

Cited by 19 publications

References 36 publications

Meis1 coordinates a network of genes implicated in eye development and microphthalmia

Meis1 coordinates a network of genes implicated in eye development and microphthalmia

NOTCH activation interferes with cell fate specification in the gastrulating mouse embryo

Sox1 Is Required for the Specification of a Novel p2-Derived Interneuron Subtype in the Mouse Ventral Spinal Cord

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