Vertebrate bHLH genes and the determination of neuronal fates

F Guillemot - Experimental cell research, 1999 - Elsevier
Experimental cell research, 1999Elsevier
The assembly of neuronal circuits requires that neurons with the appropriate phenotype are
generated at defined positions and in correct number. Rapid progress is being made in
deciphering the cellular and molecular mechanisms regulating neurogenesis in the
vertebrate nervous system [1, 2]. In vivo cell lineage tracing studies and in vitro cultures have
demonstrated the existence of various types of neural progenitor cells, including multipotent
stem cells that can generate neurons, astrocytes, and oligodendrocytes, and precursors with …
The assembly of neuronal circuits requires that neurons with the appropriate phenotype are generated at defined positions and in correct number. Rapid progress is being made in deciphering the cellular and molecular mechanisms regulating neurogenesis in the vertebrate nervous system [1, 2]. In vivo cell lineage tracing studies and in vitro cultures have demonstrated the existence of various types of neural progenitor cells, including multipotent stem cells that can generate neurons, astrocytes, and oligodendrocytes, and precursors with more restricted proliferation and differentiation potentials [3, 4]. A number of secreted molecules regulate the proliferation, lineage commitment, and/or differentiation of these different types of progenitors in culture [5], and Notch signaling has been shown to influence whether progenitors enter a differentiation pathway or remain undifferentiated [6]. A large number of transcription factors are sequentially and transiently expressed in neural precursor cells as neurogenesis proceeds. Gain-of-function studies performed in Xenopus or chick embryos and loss-of-function studies carried out in mice have implicated different transcription factor families in distinct operations. Proteins of the basic helix-loop-helix (bHLH) class have a central role in the determination of neuronal lineages in the peripheral and central nervous system and in the acquisition of pan-neuronal traits by differentiating neurons. Many phenotypic characteristics of neurons are regulated by homeodomain proteins, but bHLH factors are also involved in the specification of certain aspects of the phenotype of neurons, in particular their neurotransmitter identity, thereby coupling generic and subtype-specific subprograms of differentiation. bHLH GENES AND THE DETERMINATION OF NEURAL LINEAGES
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