Canonical Wnt signaling through Lef1 is required for hypothalamic neurogenesis

Lee, Ji Eun; Wu, Shan Fu; Goering, Lisa M.; Dorsky, Richard I.

doi:10.1242/dev.02613

Cited by 106 publications

(129 citation statements)

References 63 publications

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“…The wnt8b morpholino has been widely used and shown not to produce off-target effects (Lee et al, 2006;Knowlton et al, 2008;Russek-Blum et al, 2008;Danesin et al, 2009). The specificity of the wnt8b morpholino was confirmed here by our genetic interaction analysis and is consistent with previous reports that that this morpholino is selective for wnt8b acting through frizzled (Russek-Blom et al, 2008), downstream of foxg1 ) and upstream of lef1 (Lee et al, 2006).…”

Section: Morpholino Microinjectionssupporting

confidence: 92%

“…The specificity of the wnt8b morpholino was confirmed here by our genetic interaction analysis and is consistent with previous reports that that this morpholino is selective for wnt8b acting through frizzled (Russek-Blom et al, 2008), downstream of foxg1 ) and upstream of lef1 (Lee et al, 2006). Morpholinos were injected into the yolk of zygotes.…”

Section: Morpholino Microinjectionssupporting

confidence: 92%

“…In the diencephalon, Wnt8b signaling promotes ventral fates (Kapsimali et al, 2004) and regulates neuronal number (RussekBlum et al, 2008). Wnt8b is expressed in the dorsal telencephalon and ventral diencephalon (caudal to the commissural plate), where it is involved in patterning of the anterior-posterior neuroectoderm and telencephalon (Kelly et al, 1995;Lekven et al, 2001;Rhinn et al, 2005;Lee et al, 2006;Danesin et al, 2009). While we have shown that wnt8b regulates the expression of slit2, the downstream signaling events remain unknown.…”

Section: Discussionmentioning

confidence: 99%

“…While we have shown that wnt8b regulates the expression of slit2, the downstream signaling events remain unknown. Wnt8a has been traditionally classified as an activator of canonical/β-catenin signaling (Katoh, 2005;Lee et al, 2006) and in zebrafish has been shown to also interact with other Frizzled family members (Kim et al, 2002). In contrast, the downstream events following Fzd3 activation appear to vary depending on the developmental context which most likely reflects the Wnt ligand and co-receptors involved.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently shown that fzd3a indirectly regulates the formation of these commissures by modulating the expression of the chemorepulsive ligand slit2 . Given that wnt8b is expressed adjacent to the commissural plate and that it plays a role in forebrain patterning (Kim et al, 2000;Houart et al, 2002;Kim et al, 2002;Lee et al, 2006;Danesin et al, 2009;Paridaen et al, 2009) we reasoned that this ligand was a prime candidate for mediating Fzd3a-dependent commissural formation.…”

Section: Wnt8b Is Necessary For Formation Of the Anterior And Post-opmentioning

confidence: 99%

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Frizzled-3a and Wnt-8b genetically interact during forebrain commissural formation in embryonic zebrafish

Hofmeister

Key

2013

Brain Research

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Number of words: 3225Key words: Wnt8b, Fzd3a, axon guidance, commissure, zebrafish, slit2Keyfindings:• Knockdown of Wnt8b results in an absence of the anterior commissure and a reduction of the post-optic commissure • Knockdown of Wnt8b results in a expansion of slit2 at the rostral midline and a reduction of the glial bridge • The phenotype observed following knockdown of Wnt8b is similar to that seen following knockdown of Fzd3a • Combined loss of both Wnt8b and Fzd3a caused a synergistic increase in commissural defects and abnormal slit2 expression • Fzd3a and Wnt8b act in the same genetic pathway to control normal patterning of the commissural plate Acknowledgements: This work was supported by grants from NHMRC and ARC to B.K.2 AbstractThe commissural plate forms the rostral surface of the embryonic vertebrate forebrain and provides a cellular substrate for forebrain commissural axons. We have previously reported that the Wnt receptor frizzled-3a (fzd3a) restricts the expression of the chemorepulsive guidance ligand slit2 to a discrete domain of neuroepithelial cells in the commissural plate of embryonic zebrafish. Loss-of-Fzd3a function perturbed slit2 expression and disrupted the formation of glial bridges which guide the formation of forebrain commissures. We now show that Wnt8b is also necessary for anterior commissural formation as well as for patterning of slit2 expression at the midline. Knock down of Wnt8b produced the same phenotype as loss of Fzd3a which suggested that these genes were acting together to regulate axon guidance. Simultaneous sub-threshold knock down of both Fzd3a and Wnt8b led to a greater than additive increase in the penetrance of the mutant phenotype which indicated that these two genes were indeed interacting. We have shown here that Fzd3a/Wnt8b signaling is essential for normal patterning of the commissural plate and that loss-of-function in either receptor or ligand causes Slit2-dependent defects in glial bridge morphology which indirectly attenuated axon midline crossing in the embryonic vertebrate forebrain.3

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Section: Morpholino Microinjectionssupporting

confidence: 92%

Section: Morpholino Microinjectionssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Wnt8b Is Necessary For Formation Of the Anterior And Post-opmentioning

confidence: 99%

See 3 more Smart Citations

Frizzled-3a and Wnt-8b genetically interact during forebrain commissural formation in embryonic zebrafish

Hofmeister

Key

2013

Brain Research

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Wnt Signaling in Neural Development

Dorsky

2014

WNT Signaling in Development and Disease

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Development of the Neuroendocrine Hypothalamus

Burbridge

Stewart

Placzek

2016

Comprehensive Physiology

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The neuroendocrine hypothalamus is composed of the tuberal and anterodorsal hypothalamus, together with the median eminence/neurohypophysis. It centrally governs wide-ranging physiological processes, including homeostasis of energy balance, circadian rhythms and stress responses, as well as growth and reproductive behaviours. Homeostasis is maintained by integrating sensory inputs and effecting responses via autonomic, endocrine and behavioural outputs, over diverse time-scales and throughout the lifecourse of an individual. Here, we summarize studies that begin to reveal how different territories and cell types within the neuroendocrine hypothalamus are assembled in an integrated manner to enable function, thus supporting the organism's ability to survive and thrive. We discuss how signaling pathways and transcription factors dictate the appearance and regionalization of the hypothalamic primordium, the maintenance of progenitor cells, and their specification and differentiation into neurons. We comment on recent studies that harness such programmes for the directed differentiation of human ES/iPS cells. We summarize how developmental plasticity is maintained even into adulthood and how integration between the hypothalamus and peripheral body is established in the median eminence and neurohypophysis. Analysis of model organisms, including mouse, chick and zebrafish, provides a picture of how complex, yet elegantly coordinated, developmental programmes build glial and neuronal cells around the third ventricle of the brain. Such conserved processes enable the hypothalamus to mediate its function as a central integrating and response-control mediator for the homeostatic processes that are critical to life. Early indications suggest that deregulation of these events may underlie multifaceted pathological conditions and dysfunctional physiology in humans, such as obesity.

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Canonical Wnt signaling through Lef1 is required for hypothalamic neurogenesis

Cited by 106 publications

References 63 publications

Frizzled-3a and Wnt-8b genetically interact during forebrain commissural formation in embryonic zebrafish

Frizzled-3a and Wnt-8b genetically interact during forebrain commissural formation in embryonic zebrafish

Wnt Signaling in Neural Development

Development of the Neuroendocrine Hypothalamus

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