Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo.

Sophie R Miller,Surangi N Perera,Clare V H Baker

doi:10.1242/bio.023887

Sophie R Miller, Surangi N Perera + Show 1 more

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https://doi.org/10.1242/bio.023887

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Journal: Biology open	Publication Date: Jan 1, 2017
Citations: 11	License type: CC BY 3.0

Affiliation: University of Cambridge

Abstract

ABSTRACTPerivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain) is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs), we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1) into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

Highlights

In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crestderived olfactory ensheathing glial cells (OECs), we used in ovo electroporation to insert a tetracycline-inducible Notch E construct into the genome of chicken cranial neural crest cell precursors, and activated Notch E expression by doxycycline injection at embryonic day 4
Perivascular cells – pericytes and vascular smooth muscle cells - form the periendothelial wall of blood vessels: mature pericytes are embedded within the basement membrane of the endothelial cells in microvessels, while vascular smooth muscle cells are found in multiple layers around larger vessels
In experiments originally aimed at testing the effect on olfactory ensheathing cell (OEC) development of prematurely activating Notch1, which is normally expressed in developing chicken OECs from E5 (Miller et al, 2016), we used the Tol2 transposase/“Teton” in ovo electroporation system (Sato et al, 2007; Watanabe et al, 2007) to drive Notch∆E, encoding a constitutively active form of mouse Notch1 (Kopan et al, 1996; Sato et al, 2008), in cranial neural crest-derived cells from E4

Summary

Introduction

Perivascular (mural) cells – pericytes and vascular smooth muscle cells - form the periendothelial (outer) wall of blood vessels: mature pericytes are embedded within the basement membrane of the endothelial cells in microvessels (capillaries, terminal arterioles, postcapillary venules), while vascular smooth muscle cells are found in multiple layers around larger vessels (reviewed by Armulik et al, 2011; Majesky et al, 2011). Perivascular cells in the trunk, and many in the head, originate from mesoderm, but quail-chick chimera experiments revealed that the cranial neural crest (including the cardiac neural crest, a subset of the cranial neural crest that arises from the caudal hindbrain) provides perivascular cells to blood vessels in the face, pharyngeal arches and forebrain, including those of the retina (Le Lièvre and Le Douarin, 1975; Bergwerff et al, 1998; Etchevers et al, 2001; Korn et al, 2002) This was later supported via genetic lineage-tracing studies in mice (Jiang et al, 2000; Gage et al, 2005; Trost et al, 2013) and most recently zebrafish (Wang et al, 2014; Ando et al, 2016). This was first demonstrated in chicken, by electroporating the lateral dermomyotome with NICD (Ben-Yair and Kalcheim, 2008), and more recently in mouse, by replacing one allele of the somite-expressed gene Pax with NICD (Mayeuf-Louchart et al, 2014)

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