The bHLH Transcription Factor NeuroD Governs Photoreceptor Genesis and Regeneration Through Delta-Notch Signaling

ABSTRACTRationaleProper functionality of the circulatory system requires correct arteriovenous (AV) endothelial cell (EC) differentiation. While Notch signaling and its downstream effector Hes- Related Family bHLH Transcription Factor with YRPW Motif (Hey)2 favor arterial specification, transcription factor (TF) chicken ovalbumin upstream transcription factor 2 (Coup-TFII) inhibits canonical Notch activity to induce venous identity. However, transcriptional programs that compete with Coup-TFII to orchestrate arterial specification upstream of Notch remain largely unknown. We identified positive regulatory domain-containing protein (Prdm)16 as an arterial EC- specific TF, but its role during arterial EC specification and development remains unexplored.ObjectiveTo unravel the role of Prdm16 during arterial endothelial lineage specification and artery formation.Methods and ResultsTranscriptomic data of freshly isolated arterial and venous ECs from humans and mice revealed that Prdm16 is exclusively expressed by arterial ECs throughout development. This expression pattern was independent of hemodynamic factors and conserved in zebrafish. Accordingly, loss of prdm16 in zebrafish perturbed AV endothelial specification and caused AV malformations in an EC-autonomous manner. This coincided with reduced canonical Notch activity in arterial ECs and was amplified when prdm16 and notch pathway members were concomitantly knocked down. In vitro studies further indicated that Prdm16 not only amplified Notch signaling, but also physically and functionally interacted with Hey2 to drive proper arterial specification.ConclusionWe showed that Prdm16 plays a pivotal role during arterial development through its physical and functional interaction with canonical Notch. As both Hey2 and Prdm16 have been associated with diverse vascular disorders including migraine and atherosclerosis, Prdm16 represents an attractive new target to treat these vascular disorders.

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Faculty Opinions recommendation of bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1023116.264810 ◽

2005 ◽

Author(s):

Magdalena Goetz

Keyword(s):

Transcription Factor ◽

Bhlh Transcription Factor

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Faculty Opinions recommendation of A nonclassical bHLH Rbpj transcription factor complex is required for specification of GABAergic neurons independent of Notch signaling.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1104439.559703 ◽

2008 ◽

Author(s):

Jean-François Brunet

Keyword(s):

Transcription Factor ◽

Notch Signaling ◽

Gabaergic Neurons ◽

Transcription Factor Complex

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Faculty Opinions recommendation of Mutation of a bHLH transcription factor allowed almond domestication.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.735980063.793561372 ◽

2019 ◽

Author(s):

François Parcy

Keyword(s):

Transcription Factor ◽

Bhlh Transcription Factor

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Conserved and non-conserved functions of the rice homologs of the Arabidopsis trichome initiation-regulating MBW complex proteins

BMC Plant Biology ◽

10.1186/s12870-021-03035-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kaijie Zheng ◽

Xutong Wang ◽

Yating Wang ◽

Shucai Wang

Keyword(s):

Transcription Factor ◽

Anthocyanin Biosynthesis ◽

Transcriptional Activator ◽

Myb Transcription Factor ◽

Bhlh Transcription Factor ◽

Seed Color ◽

Transcription Activator ◽

Root Hair Formation ◽

Protoplast Transfection ◽

Mbw Complex

Abstract Background Trichome initiation in Arabidopsis is regulated by a MYB-bHLH-WD40 (MBW) transcriptional activator complex formed by the R2R3 MYB transcription factor GLABRA1 (GL1), MYB23 or MYB82, the bHLH transcription factor GLABRA3 (GL3), ENHANCER OF GLABRA3 (EGL3) or TRANSPARENT TESTA8 (TT8), and the WD40-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1). However, the functions of the rice homologs of the MBW complex proteins remained uncharacterized. Results Based on amino acid sequence identity and similarity, and protein interaction prediction, we identified OsGL1s, OsGL3s and OsTTG1s as rice homologs of the MBW complex proteins. By using protoplast transfection, we show that OsGL1D, OsGL1E, OsGL3B and OsTTG1A were predominantly localized in the nucleus, OsGL3B functions as a transcriptional activator and is able to interact with GL1 and TTG1. By using yeast two-hybrid and protoplast transfection assays, we show that OsGL3B is able to interact with OsGL1E and OsTTG1A, and OsGL1E and OsTTG1A are also able to interact with GL3. On the other hand, we found that OsGL1D functions as a transcription activator, and it can interact with GL3 but not OsGL3B. Furthermore, our results show that expression of OsTTG1A in the ttg1 mutant restored the phenotypes including alternations in trichome and root hair formation, seed color, mucilage production and anthocyanin biosynthesis, indicating that OsTTG1A and TTG1 may have similar functions. Conclusion These results suggest that the rice homologs of the Arabidopsis MBW complex proteins are able to form MBW complexes, but may have conserved and non-conserved functions.

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