Regional Morphogenesis in the Hypothalamus: A BMP-Tbx2 Pathway Coordinates Fate and Proliferation through Shh Downregulation

Manning, Liz; Ohyama, Katsumi; Saeger, Bernhard; Hatano, Osamu; Wilson, Stuart A.; Logan, Malcolm; Placzek, Marysia

doi:10.1016/j.devcel.2006.09.021

Cited by 134 publications

(210 citation statements)

References 54 publications

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“…Neural Shh in hypothalamic precursor expansion and neurogenesis Shh is needed early for proliferation in the diencephalon (Ishibashi and McMahon, 2002) and in particular in the caudal regions (Manning et al, 2006), which agrees with the reduced size of the hypothalamus in our mutant already at E9.5 (Fig. 3B).…”

Section: Discussionsupporting

confidence: 86%

Role of NeuroepithelialSonic hedgehogin Hypothalamic Patterning

et al. 2009

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The hypothalamus is a region of the diencephalon with particularly complex patterning. Sonic hedgehog (Shh), encoding a protein with key developmental roles, shows a peculiar and dynamic diencephalic expression pattern. Here, we use transgenic strategies and in vitro experiments to test the hypothesis that Shh expressed in the diencephalic neuroepithelium (neural Shh) coordinates tissue growth and patterning in the hypothalamus. Our results show that neural Shh coordinates anteroposterior and dorsoventral patterning in the hypothalamus and in the diencephalon-telencephalon junction. Neural Shh also coordinates mediolateral hypothalamic patterning, since it is necessary for the lateral hypothalamus to attain proper size and is required for the specification of hypocretin/orexin cells. Finally, neural Shh is necessary to maintain expression of differentiation markers including survival factor Foxb1.

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Section: Discussionsupporting

confidence: 86%

Role of NeuroepithelialSonic hedgehogin Hypothalamic Patterning

et al. 2009

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“…Injection of E13.5 mouse embryos with an hybridoma producing a Shh-blocking antibody (and analyzed at E18.5) alters the distribution of RGC axons at the optic chiasm with an enlargement of the overall region occupied by RGC fibers at the midline and axon extension in aberrant directions. However, as Shh activity is important to pattern the midbrain regions surrounding the ventral hypothalamus (just adjacent to the optic chiasm) during retinal axon development (Dale et al, 1997;Barresi et al, 2005;Manning et al, 2006), it is likely that blocking Shh signaling for 5 d in developing embryos can cause patterning defects. Thus, as noted by the authors (Sánchez-Camacho and Bovolenta, 2008), it is possible that the effects observed are not due to a direct guidance effect of Shh but rather to changes in expression of other guidance cues.…”

Section: The Roles Of Shh In the Guidance Of Rgc Axonsmentioning

confidence: 99%

Segregation of Ipsilateral Retinal Ganglion Cell Axons at the Optic Chiasm Requires the Shh Receptor Boc

Fabre

Shimogori²,

Charron³

2010

J. Neurosci.

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The pattern of contralaterally and ipsilaterally projecting retinal ganglion cell (RGC) axons at the optic chiasm is essential for the establishment of binocular vision. Contralateral axons cross the chiasm midline as they progress from the optic nerve to the optic tract. In contrast, ipsilateral axons deviate from the chiasm and continue in the ipsilateral optic tract, avoiding the chiasm midline. The molecular mechanism underlying this phenomenon is not completely understood. Here we show that the Sonic Hedgehog (Shh) receptor Boc is enriched in ipsilateral RGCs of the developing retina. Together with the presence of Shh at the midline, this complementary expression pattern led us to hypothesize that Shh might repel ipsilateral RGC axons at the chiasm. Consistent with this hypothesis, we found that only Boc-positive RGC axons retract in vitro in response to Shh and that this response is lost in Boc mutant RGCs. In vivo, we show that Boc is required for the normal segregation of ipsilateral axons at the optic chiasm and, conversely, that Boc expression in contralateral RGCs prevents their axons from crossing the optic chiasm. Together, these results suggest that Shh repels ipsilateral RGC axons at the optic chiasm via its receptor Boc. This work identifies a novel molecular pathway required for the segregation of axons at the optic chiasm.

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“…Wnt signaling also governs regionalization of the nascent hypothalamus, directing the emergence of posterior (mamillary) hypothalamus throughout development, Shh and multiple different bone morphogenetic proteins (BMPs) show dynamic spatio-temporal profiles. Expression of Shh and Shh signaling components is negatively regulated by BMP signaling (Manning et al, 2006;Ohyama et al, 2008). Studies in the limb bud show that cross talk between the BMP and Shh pathways is critical for integrated growth, pattern, and differentiation (Bénazet et al, 2009), and raises the possibility that a similar cross talk between BMP and Shh signaling regulates proliferation and spatial patterning of hypothalamic neural progenitors in a concerted manner.…”

Section: Patterning Of Developing Thalamus and Hypothalamus By Secretmentioning

confidence: 99%

Molecular Pathways Controlling Development of Thalamus and Hypothalamus: From Neural Specification to Circuit Formation

et al. 2010

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The embryonic diencephalon gives rise to the vertebrate thalamus and hypothalamus, which play essential roles in sensory information processing and control of physiological homeostasis and behavior, respectively. In this review, we present new steps toward characterizing the molecular pathways that control development of these structures, based on findings in a variety of model organisms. We highlight advances in understanding how early regional patterning is orchestrated through the action of secreted signaling molecules such as Sonic hedgehog and fibroblast growth factors. We address the role of individual transcription factors in control of the regional identity and neural differentiation within the developing diencephalon, emphasizing the contribution of recent large-scale gene expression studies in providing an extensive catalog of candidate regulators of hypothalamic neural cell fate specification. Finally, we evaluate the molecular mechanisms involved in the experience-dependent development of both thalamo-cortical and hypothalamic neural circuitry. IntroductionThe developing vertebrate forebrain consists of two major parts: the telencephalon-which gives rise to cerebral cortex, striatum, amygdala, and associated structures-and the diencephalon. The diencephalon gives rise to two essential brain regions, the thalamus and hypothalamus (Fig. 1 A). Though both structures are derived from a common region of the anterior neural tube, they serve very different physiological functions. The thalamus acts as a central integrator of sensory information, receiving afferents from receptors of all sensory modalities save olfaction, and serves as the sole path by which integrated sensory information reaches the cerebral cortex and gives rise to conscious perception. The hypothalamus, on the other hand, serves a more diverse range of functions. It is a central regulator of critical homeostatic physiological processes, including temperature regulation, food intake,

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Regional Morphogenesis in the Hypothalamus: A BMP-Tbx2 Pathway Coordinates Fate and Proliferation through Shh Downregulation

Cited by 134 publications

References 54 publications

Role of NeuroepithelialSonic hedgehogin Hypothalamic Patterning

Role of NeuroepithelialSonic hedgehogin Hypothalamic Patterning

Segregation of Ipsilateral Retinal Ganglion Cell Axons at the Optic Chiasm Requires the Shh Receptor Boc

Molecular Pathways Controlling Development of Thalamus and Hypothalamus: From Neural Specification to Circuit Formation

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