Sonic hedgehog signaling at gastrula stages specifies ventral telencephalic cells in the chick embryo

Gunhaga, Lena; Jessell, Thomas M.; Edlund, Thomas

doi:10.1242/dev.127.15.3283

Cited by 90 publications

(4 citation statements)

References 64 publications

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“…Previous studies have shown that Shh can repress Pax6 expression in diverse tissues including the telencephalon [134,150,155,172,173,174]. The fact that Shh levels are highest in ventral telencephalon from the earliest stages of its development is likely to be a major factor establishing the ventral-low versus dorsal-high difference in Pax6's expression levels [175][176][177][178]. Our findings indicate that, as dorsal telencephalic development progresses, its high levels of Pax6 repress the potential actions of morphogens including Shh itself, thereby opening a time window for the unhindered production of a normal complement of cortical excitatory neurons.…”

Section: Pax6's Effects On Shh Signaling Might Control the Timing Of ...mentioning

confidence: 99%

Pax6 limits the competence of developing cerebral cortical cells to respond to inductive intercellular signals

et al. 2022

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The development of stable specialized cell types in multicellular organisms relies on mechanisms controlling inductive intercellular signals and the competence of cells to respond to such signals. In developing cerebral cortex, progenitors generate only glutamatergic excitatory neurons despite being exposed to signals with the potential to initiate the production of other neuronal types, suggesting that their competence is limited. Here, we tested the hypothesis that this limitation is due to their expression of transcription factor Pax6. We used bulk and single-cell RNAseq to show that conditional cortex-specific Pax6 deletion from the onset of cortical neurogenesis allowed some progenitors to generate abnormal lineages resembling those normally found outside the cortex. Analysis of selected gene expression showed that the changes occurred in specific spatiotemporal patterns. We then compared the responses of control and Pax6-deleted cortical cells to in vivo and in vitro manipulations of extracellular signals. We found that Pax6 loss increased cortical progenitors’ competence to generate inappropriate lineages in response to extracellular factors normally present in developing cortex, including the morphogens Shh and Bmp4. Regional variation in the levels of these factors could explain spatiotemporal patterns of fate change following Pax6 deletion in vivo. We propose that Pax6’s main role in developing cortical cells is to minimize the risk of their development being derailed by the potential side effects of morphogens engaged contemporaneously in other essential functions.

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Section: Pax6's Effects On Shh Signaling Might Control the Timing Of ...mentioning

confidence: 99%

Pax6 limits the competence of developing cerebral cortical cells to respond to inductive intercellular signals

et al. 2022

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“…Shh is involved in the patterning of the ventral telencephalon and directly regulates the expression of transcription factors required to specify ventral cell fates such as Nkx2.1 [72][73][74]. Results obtain from the analysis of Shh-null mice also support a role for Shh in regional specification of the ventral telencephalon [31,75].…”

Section: Anterior Shh Sources In the Neural Axismentioning

confidence: 84%

Establishing Hedgehog Gradients during Neural Development

Douceau

Guerrero

Ferent

2023

Cells

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A morphogen is a signaling molecule that induces specific cellular responses depending on its local concentration. The concept of morphogenic gradients has been a central paradigm of developmental biology for decades. Sonic Hedgehog (Shh) is one of the most important morphogens that displays pleiotropic functions during embryonic development, ranging from neuronal patterning to axon guidance. It is commonly accepted that Shh is distributed in a gradient in several tissues from different origins during development; however, how these gradients are formed and maintained at the cellular and molecular levels is still the center of a great deal of research. In this review, we first explored all of the different sources of Shh during the development of the nervous system. Then, we detailed how these sources can distribute Shh in the surrounding tissues via a variety of mechanisms. Finally, we addressed how disrupting Shh distribution and gradients can induce severe neurodevelopmental disorders and cancers. Although the concept of gradient has been central in the field of neurodevelopment since the fifties, we also describe how contemporary leading-edge techniques, such as organoids, can revisit this classical model.

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“…Previous studies have shown that Shh can repress Pax6 expression in diverse tissues including the telencephalon (Macdonald et al, 1995; Ericson et al, 1997; Rallu et al, 2002; Danjo et al, 2011; Robertshaw et al, 2013; Yabut et al, 2020). The fact that Shh levels are highest in ventral telencephalon from the earliest stages of its development is likely to be a major factor establishing the ventral-low versus dorsal-high difference in Pax6 ’s expression levels (Echelard et al, 1993; Shimamura et al, 1995; Gunhaga et al, 2000; Rallu et al, 2002b). Our findings indicate that, as dorsal telencephalic development progresses, its high levels of Pax6 repress the potential actions of morphogens including Shh itself, thereby opening a time-window for the unhindered production of a normal complement of cortical excitatory neurons.…”

Section: Discussionmentioning

confidence: 99%

Pax6 Limits the Competence of Developing Cerebral Cortical Cells

Manuel

Tan

Kozić

et al. 2022

Preprint

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The development of stable specialized cell types in multicellular organisms relies on mechanisms controlling inductive intercellular signals and the competence of cells to respond to such signals. In developing cerebral cortex, progenitors generate only glutamatergic excitatory neurons despite being exposed to signals with the potential to initiate the production of other neuronal types, suggesting that their competence is limited. Here we tested the hypothesis that this limitation is due to their expression of transcription factor Pax6. We used bulk and single cell RNAseq to show that conditional cortex-specific Pax6 deletion from the onset of cortical neurogenesis allowed some progenitors to generate abnormal lineages resembling those normally found outside the cortex. Analysis of selected gene expression showed that the changes occurred in specific spatiotemporal patterns. We then compared the responses of control and Pax6-deleted cortical cells to in vivo and in vitro manipulations of extracellular signals. We found that Pax6 loss increased cortical progenitors’ competence to generate inappropriate lineages in response to extracellular factors normally present in developing cortex, including the morphogens Shh and Bmp4. Regional variation in the levels of these factors could explain spatiotemporal patterns of fate change following Pax6 deletion in vivo. We propose that Pax6’s main role in developing cortical cells is to minimize the risk of their development being derailed by the potential side-effects of morphogens engaged contemporaneously in other essential functions.

show abstract

Sonic hedgehog signaling at gastrula stages specifies ventral telencephalic cells in the chick embryo

Cited by 90 publications

References 64 publications

Pax6 limits the competence of developing cerebral cortical cells to respond to inductive intercellular signals

Pax6 limits the competence of developing cerebral cortical cells to respond to inductive intercellular signals

Establishing Hedgehog Gradients during Neural Development

Pax6 Limits the Competence of Developing Cerebral Cortical Cells

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