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Sonic hedgehog is not a limb morphogen but acts as a trigger to specify all digits in mice

  1. Author:
    Zhu, Jianjian
    Patel,Rashmi
    Trofka, Anna
    Harfe, Brian D
    Mackem,Susan

  2. Author Address

    Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI, Frederick, MD, USA., College of Medicine, Department of Molecular Genetics and Microbiology and the Genetics Institute, University of Florida, Gainesville, FL, USA., Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI, Frederick, MD, USA. Electronic address: mackems@mail.nih.gov.,
    1. Year: 2022
    2. Date: Aug 13
    3. Epub Date: 2022 08 13
  2. Journal: Developmental Cell
    1. 57
    2. 17
    3. Pages: 2048-2062
  4. Type of Article: Article
  1. Abstract:

    Limb patterning by Sonic hedgehog (Shh), via either graded spatial or temporal signal integration, is a paradigm for "morphogen" function, yet how Shh instructs distinct digit identities remains controversial. Here, we bypass the Shh requirement in cell survival during outgrowth and demonstrate that a transient, early Shh pulse is both necessary and sufficient for normal mouse limb development. Shh response is only short range and is limited to the Shh-expressing zone during this time window. Shh patterns digits 1-3, anterior to this zone, by an indirect mechanism rather than direct spatial or temporal signal integration. Using a genetic relay-signaling assay, we discover that Shh also specifies digit 1/thumb (thought to be exclusively Shh independent) indirectly, and this finding implicates Shh in a unique regulatory hierarchy for digit 1 evolutionary adaptations such as opposable thumbs. This study illuminates Shh as a trigger for an indirect downstream network that becomes rapidly self-sustaining, with mechanistic relevance for limb development, regeneration, and evolution. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.devcel.2022.07.016
  3. PMID: 35977544
  4. View record in Web of Science®
  5. WOS: 000898457200004
  6. PII : S1534-5807(22)00547-0

Library Notes

  1. Fiscal Year: FY2021-2022
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