XCoe2, a transcription factor of the Col/Olf-1/EBF family involved in the specification of primary neurons in Xenopus

• Published in: Current biology 1998-02, Vol.8 (4), p.199-209
• Main Authors: Dubois, Laurence, Bally-Cuif, Laure, Crozatier, Michele, Moreau, Jacques, Paquereau, Laurent, Vincent, Alain
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Basic Helix-Loop-Helix Transcription Factors; DNA, Complementary; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drosophila; Gene Expression Regulation, Developmental; Helix-Loop-Helix Motifs; Mice; Models, Biological; Molecular Sequence Data; Nerve Tissue Proteins - genetics; Nervous System - cytology; Nervous System - embryology; Neurons - cytology; Signal Transduction; Trans-Activators - chemistry; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Activation; Tubulin - genetics; Xenopus; Xenopus Proteins
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/S0960-9822(98)70084-3

Background: Primary neurogenesis in Xenopus is a model for studying the control of neural cell fate decisions. The specification of primary neurons appears to be driven by transcription factors containing a basic region and a helix–loop–helix (HLH) motif: expression of Xenopus neurogenin-related-1 (X-ngnr-1) defines the three prospective domains of primary neurogenesis, and expression of XNeuroD coincides with neuronal differentiation. The transition between neuronal competence and stable commitment to a neuronal fate remains poorly characterised, however. Results:Drosophila Collier and rodent early B-cell factor/olfactory-1 define a family of HLH transcription factors containing a previously unknown type of DNA-binding domain. We isolated an orthologous gene from Xenopus, Xcoe2, which is expressed in precursors of primary neurons. Xcoe2 is transcribed after X-ngnr-1 and before XNeuroD. Overexpression of a dominant-negative mutant of XCoe2 prevented neuronal differentiation. Conversely, overexpressed wild-type Xcoe2 could promote ectopic differentiation of neurons, in both the neural plate and the epidermis. In contrast to studies with X-ngnr-1 or XNeuroD, the supernumerary neurons induced by Xcoe2 appeared in a ‘salt-and-pepper’ pattern, resulting from the activation of X-Delta 1 expression and feedback regulation by lateral inhibition. Conclusions: XCoe2 may play a pivotal role in the transcriptional cascade that specifies primary neurons in Xenopus embryos: by maintaining Delta–Notch signalling, XCoe2 stabilises the higher neural potential of selected progenitor cells that express X-ngnr-1, ensuring the transition between neural competence and irreversible commitment to a neural fate; and it promotes neuronal differentiation by activating XNeuroD expression, directly or indirectly.