Lineage restriction maintains a stable organizer cell population at the zebrafish midbrain-hindbrain boundary

Langenberg, Tobias; Brand, Michael

doi:10.1242/dev.01862

Cited by 44 publications

(36 citation statements)

References 43 publications

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“…Therefore, the MHB boundary is coupled with the heritable expression of Gbx2 in r1 cells. Our findings are in agreement with a previous report that suggested that lineage restriction is probably established at the MHB at the end of gastrulation in zebrafish (Langenberg and Brand, 2005). A GIFM study using a Wnt1-CreER transgenic mouse line to label mes cells suggests that lineage restriction may not occur in either the alar plate until E8.5, or in the basal plate until E9.5 (Zervas et al, 2004).…”

Section: Previous Studies Have Demonstrated That Mutual Inhibition Besupporting

confidence: 93%

Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary

Sunmonu

Guo

2011

Development

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SUMMARYIn vertebrates, the common expression border of two homeobox genes, Otx2 and Gbx2, demarcates the prospective midbrainhindbrain border (MHB) in the neural plate at the end of gastrulation. The presence of a compartment boundary at the MHB has been demonstrated, but the mechanism and timing of its formation remain unclear. We show by genetic inducible fate mapping using a Gbx2CreER knock-in mouse line that descendants of Gbx2 + cells as early as embryonic day (E) 7.5 do not cross the MHB. Without Gbx2, hindbrain-born cells abnormally populate the entire midbrain, demonstrating that Gbx2 is essential for specifying hindbrain fate. Gbx2 + and Otx2 + cells segregate from each other, suggesting that mutually exclusive expression of Otx2 and Gbx2 in midbrain and hindbrain progenitors is responsible for cell sorting in establishing the MHB. The MHB organizer gene Fgf8, which is expressed as a sharp transverse band immediately posterior to the lineage boundary at the MHB, is crucial in maintaining the lineage-restricted boundary after E7.5. Partial deletion of Fgf8 disrupts MHB lineage separation. Activation of FGF pathways has a cell-autonomous effect on cell sorting in midbrain progenitors. Therefore, Fgf8 from the MHB may signal the nearby mesencephalic cells to impart distinct cell surface characteristics or induce local cell-cell signaling, which consequently prevents cell movements across the MHB. Our findings reveal the distinct function of Gbx2 and Fgf8 in a stepwise process in the development of the compartment boundary at the MHB and that Fgf8, in addition to its organizer function, plays a crucial role in maintaining the lineage boundary at the MHB by restricting cell movement.

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Section: Previous Studies Have Demonstrated That Mutual Inhibition Besupporting

confidence: 93%

Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary

Sunmonu

Guo

2011

Development

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“…Besides the involvement of Otx proteins, the two signalling centres also each release a combination of signal molecules (ZLI: Wnt8b and Shh; MHB: Wnt1 and Fgf8). The boundary between the midbrain and hindbrain has lineagerestriction properties (Zervas et al, 2004;Langenberg and Brand, 2005), whereas the ZLI is a narrow stripe of cells defined by both an anterior and a posterior lineage-restriction boundary . Therefore, because the ZLI is a zone rather than an interface, we considered whether the position of its prethalamic border is set independently of its thalamic border.…”

Section: Independent Positioning Of the Anterior And Posterior Zli Bomentioning

confidence: 99%

Otx1l, Otx2 and Irx1b establish and position the ZLI in the diencephalon

et al. 2007

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The thalamic complex is the major sensory relay station in the vertebrate brain and comprises three developmental subregions: the prethalamus, the thalamus and an intervening boundary region -the zona limitans intrathalamica (ZLI). Shh signalling from the ZLI confers regional identity of the flanking subregions of the ZLI, making it an important local signalling centre for regional differentiation of the diencephalon. However, our understanding of the mechanisms responsible for positioning the ZLI along the neural axis is poor. Here we show that, before ZLI formation, both Otx1l and Otx2 (collectively referred to as Otx1l/2) are expressed in spatially restricted domains. Formation of both the ZLI and the Irx1b-positive thalamus require Otx1l/2; embryos impaired in Otx1l/2 function fail to form these areas, and, instead, the adjacent pretectum and, to a lesser extent, the prethalamus expand into the mis-specified area. Conditional expression of Otx2 in these morphant embryos cell-autonomously rescues the formation of the ZLI at its correct location. Furthermore, absence of thalamic Irx1b expression, in the presence of normal Otx1l/2 function, leads to a substantial caudal broadening of the ZLI by transformation of thalamic precursors. We therefore propose that the ZLI is induced within the competence area established by Otx1l/2, and is posteriorly restricted by Irx1b.

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“…In recent years, it has become increasingly clear that the boundaries of such lineage restriction compartments function as bi-directional signalling centres (Kiecker and Lumsden, 2005). Thus, for example, the midbrain-hindbrain boundary (Langenberg and Brand, 2005;Zervas et al, 2004) and the zona limitans intrathalamica (ZLI) ) pattern adjacent neuroepithelium. In this study, we used the precedent of the experimental approaches taken by these studies to determine whether such a signalling centre is maintained at the boundary between the roof plate and the neuroepithelium.…”

Section: Introductionmentioning

confidence: 99%

The roof plate boundary is a bi-directional organiser of dorsal neural tube and choroid plexus development

et al. 2012

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SUMMARYThe roof plate is a signalling centre positioned at the dorsal midline of the central nervous system and generates dorsalising morphogenic signals along the length of the neuraxis. Within cranial ventricles, the roof plate gives rise to choroid plexus, which regulates the internal environment of the developing and adult brain and spinal cord via the secretion of cerebrospinal fluid. Using the fourth ventricle as our model, we show that the organiser properties of the roof plate are determined by its boundaries with the adjacent neuroepithelium. Through a combination of in ovo transplantation, co-culture and electroporation techniques in chick embryos between embryonic days 3 and 6, we demonstrate that organiser properties are maintained by interactions between the non-neural roof plate and the neural rhombic lip. At the molecular level, this interaction is mediated by Delta-Notch signalling and upregulation of the chick homologue of Hes1: chairy2. Gain-and loss-of-function approaches reveal that cdelta1 is both necessary and sufficient for organiser function. Our results also demonstrate that while chairy2 is specifically required for the maintenance of the organiser, its ectopic expression is not sufficient to recapitulate organiser properties. Expression of atonal1 in the rhombic lip adjacent at the roof plate boundary is acutely dependent on both boundary cell interactions and Delta-Notch signalling. Correspondingly, the roof plate boundary organiser also signals to the roof plate itself to specify the expression of early choroid plexus markers. Thus, the roof plate boundary organiser signals bi-directionally to acutely coordinate the development of adjacent neural and non-neural tissues.

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Lineage restriction maintains a stable organizer cell population at the zebrafish midbrain-hindbrain boundary

Cited by 44 publications

References 43 publications

Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary

Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary

Otx1l, Otx2 and Irx1b establish and position the ZLI in the diencephalon

The roof plate boundary is a bi-directional organiser of dorsal neural tube and choroid plexus development

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