Evidence map›Paper›PMID 40986357›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Dual Bmp-negative feedback loops modulate function of both AER and ZPA to buffer and constrain postaxial digit number.

Rashmi Patel, Susan Mackem

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Rashmi PatelCancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Susan MackemCancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.ORCID 0000-0002-9095-9914

Funding

HHS | NIH | NCI | Center for Cancer Research (CCR) ZIA BC 011118 011119 011120
6 · The paper itself

Abstract

Several lines of evidence indicate that posterior (postaxial) digit number in tetrapod vertebrates is constrained to the pentadactyl state by interactions between the two major signaling centers that organize digit pattern and growth, the Sonic hedgehog (Shh)-expressing Zone of Polarizing Activity (ZPA) and the Fgf-expressing Apical Ectodermal Ridge (AER) ectoderm. Negative short-range effects of Shh on the immediately overlying AER limit its posterior extent and function, either by direct Shh signaling or with Bmps playing a key role. How this strong inhibitory effect is counterbalanced to maintain pentadactyly in many vertebrate species remains less clear. In this study, we used genetic approaches in mice to reevaluate the mechanism by which Shh signaling modulates AER function and demonstrate that this occurs via Shh-target Bmps that act as a relay signal, rather than by direct Shh action. Furthermore, we show that Shh-induced Bmps also act directly on the ZPA, in a negative feedback loop, to down-regulate

Indexed as

Body PatterningBone Morphogenetic ProteinsEctodermExtremitiesHedgehog ProteinsAnimalsFeedback, PhysiologicalFemaleFibroblast Growth FactorsGene Expression Regulation, DevelopmentalMaleMiceMice, TransgenicSignal TransductionBone Morphogenetic ProteinsFibroblast Growth FactorsHedgehog ProteinsShh protein, mouseBmpsdigit patterninglimb developmentnegative feedbackSonic hedgehog

Identifiers

PMID40986357
PMCPMC12501167

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.