ArticleDevelopmental biology2012
A novel role for FOXA2 and SHH in organizing midbrain signaling centers.
Article in Developmental biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
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- Expression patterns of key Sonic Hedgehog signaling pathway components in the developing and adult mouse midbrain and in the MN9D cell line.Cell and tissue research · 2017Article
- Embryonic development of selectively vulnerable neurons in Parkinson's disease.NPJ Parkinson's disease · 2017Review
- Cell-cycle-dependent TGFβ-BMP antagonism regulates neural tube closure by modulating tight junctions.Journal of cell science · 2017Article
- Selective Generation of Dopaminergic Precursors from Mouse Fibroblasts by Direct Lineage Conversion.Scientific reports · 2015Article
- Glycoconjugates distribution during developing mouse spinal cord motor organizers.Iranian biomedical journal · 2015Article
- Activated astrocytes enhance the dopaminergic differentiation of stem cells and promote brain repair through bFGF.Nature communications · 2014Article
- Selection Based on FOXA2 Expression Is Not Sufficient to Enrich for Dopamine Neurons From Human Pluripotent Stem Cells.Stem cells translational medicine · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The floor plate (FP) is a midline signaling center, known to direct ventral cell fates and axon guidance in the neural tube. The recent identification of midbrain FP as a source of dopaminergic neurons has renewed interest in its specification and organization, which remain poorly understood. In this study, we have examined the chick midbrain and spinal FP and show that both can be partitioned into medial (MFP) and lateral (LFP) subdivisions. Although Hedgehog (HH) signaling is necessary and sufficient for LFP specification, it is not sufficient for MFP induction. By contrast, the transcription factor FOXA2 can execute the full midbrain and spinal cord FP program via HH-independent and dependent mechanisms. Interestingly, although HH-independent FOXA2 activity is necessary and sufficient for inducing MFP-specific gene expression (e.g., LMX1B, BMP7), it cannot confer ventral identity to midline cells without also turning on Sonic hedgehog (SHH). We also note that the signaling centers of the midbrain, the FP, roof plate (RP) and the midbrain-hindbrain boundary (MHB) are physically contiguous, with each expressing LMX1B and BMP7. Possibly as a result, SHH or FOXA2 misexpression can transform the MHB into FP and also suppress RP induction. Conversely, HH or FOXA2 knockdown expands the endogenous RP and transforms the MFP into a RP and/or MHB fate. Finally, combined HH blockade and FOXA2 misexpression in ventral midbrain induces LMX1B expression, which triggers the specification of the RP, rather than the MFP. Thus we identify HH-independent and dependent roles for FOXA2 in specifying the FP. In addition, we elucidate for the first time, a novel role for SHH in determining whether a midbrain signaling center will become the FP, MHB or RP.
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Registered trials
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 OpenQuestion graph.