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Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis

An important question in organogenesis is how tissue-specific transcription factors interact with signaling pathways. In some cases, transcription factors define the context for how signaling pathways elicit tissue- or cell-specific responses, and in others, they influence signaling through transcri...

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Autores principales: Li, Xiaodong, Gordon, Patrick J, Gaynes, John A, Fuller, Alexandra W, Ringuette, Randy, Santiago, Clayton P, Wallace, Valerie, Blackshaw, Seth, Li, Pulin, Levine, Edward M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718532/
https://www.ncbi.nlm.nih.gov/pubmed/36459481
http://dx.doi.org/10.7554/eLife.78342
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author Li, Xiaodong
Gordon, Patrick J
Gaynes, John A
Fuller, Alexandra W
Ringuette, Randy
Santiago, Clayton P
Wallace, Valerie
Blackshaw, Seth
Li, Pulin
Levine, Edward M
author_facet Li, Xiaodong
Gordon, Patrick J
Gaynes, John A
Fuller, Alexandra W
Ringuette, Randy
Santiago, Clayton P
Wallace, Valerie
Blackshaw, Seth
Li, Pulin
Levine, Edward M
author_sort Li, Xiaodong
collection PubMed
description An important question in organogenesis is how tissue-specific transcription factors interact with signaling pathways. In some cases, transcription factors define the context for how signaling pathways elicit tissue- or cell-specific responses, and in others, they influence signaling through transcriptional regulation of signaling components or accessory factors. We previously showed that during optic vesicle patterning, the Lim-homeodomain transcription factor Lhx2 has a contextual role by linking the Sonic Hedgehog (Shh) pathway to downstream targets without regulating the pathway itself. Here, we show that during early retinal neurogenesis in mice, Lhx2 is a multilevel regulator of Shh signaling. Specifically, Lhx2 acts cell autonomously to control the expression of pathway genes required for efficient activation and maintenance of signaling in retinal progenitor cells. The Shh co-receptors Cdon and Gas1 are candidate direct targets of Lhx2 that mediate pathway activation, whereas Lhx2 directly or indirectly promotes the expression of other pathway components important for activation and sustained signaling. We also provide genetic evidence suggesting that Lhx2 has a contextual role by linking the Shh pathway to downstream targets. Through these interactions, Lhx2 establishes the competence for Shh signaling in retinal progenitors and the context for the pathway to promote early retinal neurogenesis. The temporally distinct interactions between Lhx2 and the Shh pathway in retinal development illustrate how transcription factors and signaling pathways adapt to meet stage-dependent requirements of tissue formation.
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spelling pubmed-97185322022-12-03 Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis Li, Xiaodong Gordon, Patrick J Gaynes, John A Fuller, Alexandra W Ringuette, Randy Santiago, Clayton P Wallace, Valerie Blackshaw, Seth Li, Pulin Levine, Edward M eLife Developmental Biology An important question in organogenesis is how tissue-specific transcription factors interact with signaling pathways. In some cases, transcription factors define the context for how signaling pathways elicit tissue- or cell-specific responses, and in others, they influence signaling through transcriptional regulation of signaling components or accessory factors. We previously showed that during optic vesicle patterning, the Lim-homeodomain transcription factor Lhx2 has a contextual role by linking the Sonic Hedgehog (Shh) pathway to downstream targets without regulating the pathway itself. Here, we show that during early retinal neurogenesis in mice, Lhx2 is a multilevel regulator of Shh signaling. Specifically, Lhx2 acts cell autonomously to control the expression of pathway genes required for efficient activation and maintenance of signaling in retinal progenitor cells. The Shh co-receptors Cdon and Gas1 are candidate direct targets of Lhx2 that mediate pathway activation, whereas Lhx2 directly or indirectly promotes the expression of other pathway components important for activation and sustained signaling. We also provide genetic evidence suggesting that Lhx2 has a contextual role by linking the Shh pathway to downstream targets. Through these interactions, Lhx2 establishes the competence for Shh signaling in retinal progenitors and the context for the pathway to promote early retinal neurogenesis. The temporally distinct interactions between Lhx2 and the Shh pathway in retinal development illustrate how transcription factors and signaling pathways adapt to meet stage-dependent requirements of tissue formation. eLife Sciences Publications, Ltd 2022-12-02 /pmc/articles/PMC9718532/ /pubmed/36459481 http://dx.doi.org/10.7554/eLife.78342 Text en © 2022, Li et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Li, Xiaodong
Gordon, Patrick J
Gaynes, John A
Fuller, Alexandra W
Ringuette, Randy
Santiago, Clayton P
Wallace, Valerie
Blackshaw, Seth
Li, Pulin
Levine, Edward M
Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis
title Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis
title_full Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis
title_fullStr Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis
title_full_unstemmed Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis
title_short Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis
title_sort lhx2 is a progenitor-intrinsic modulator of sonic hedgehog signaling during early retinal neurogenesis
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718532/
https://www.ncbi.nlm.nih.gov/pubmed/36459481
http://dx.doi.org/10.7554/eLife.78342
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