Basic helix-loop-helix genes in neural development

doi:10.1016/S0959-4388(97)80115-8

Current Opinion in Neurobiology

Volume 7, Issue 1, February 1997, Pages 13-20

https://doi.org/10.1016/S0959-4388(97)80115-8 Get rights and content

Abstract

Several major advances in the understanding of the regulation of vertebrate neurogenesis by members of the basic helix-loop-helix (bHLH) protein family have been made in the past year. Specifically, a number of bHLH genes have been cloned and shown to convert non-neuronal fate to neuronal fate when expressed ectopically. In particular, studies on NeuroD and Neurogenin suggest a regulatory pathway, providing powerful molecular tools to study vertebrate neurogenesis.

References (45)

H Weintraub
The MyoD family and myogenesis: redundancy, networks, and thresholds
Cell
(1993)
YN Jan et al.
HLH proteins, fly neurogenesis, and vertebrate myogenesis
Cell
(1993)
C Porcher et al.
The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages
Cell
(1996)
F Guillemot et al.
Mammalian achaete-scute homolog-1 is required for the early development of olfactory and autonomic neurons
Cell
(1993)
R Burgess et al.
Paraxis: a basic helix-loop-helix protein expressed in paraxial mesoderm and developing somites
Dev Biol
(1995)
L Li et al.
Dermo-1: a novel twist-related bHLH protein expressed in the developing dermis
Dev Biol
(1995)
C Murre et al.
Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence
Cell
(1989)
F Guillemot et al.
Dynamic expression of the murine Achaete-Scute homologue Mash1 in the developing nervous system
Mech Dev
(1993)
C Akazawa et al.
A mammalian helix-loop-helix factor structurally related to the product of Drosophila proneural gene atonal is a positive transcriptional regulator expressed in the developing nervous system
J Biol Chem
(1995)
A Bartholomä et al.
NEX-1: a novel brain-specific helix-loop-helix protein with autoregulation and sustained expression in mature cortical neurons
Mech Dev
(1994)

L Sommer et al.

neurogenins, a novel family of atonal-related bHLH transcription factors, are putative mammalian neuronal determination genes that reveal progenitor cell heterogeneity in the developing CNS and PNS

Mol Cell Neurosci

(1996)

CG Begley et al.

Molecular characterization of NSCL, a gene encoding a helix-loop-helix protein expressed in the developing nervous system

Proc Natl Acad Sci USA

(1992)

JE Lee et al.

Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein

Science

(1995)

M Ishibashi et al.

Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects

Genes Dev

(1995)

T Neuman et al.

Neuronal expression of regulatory helix-loop-helix factor Id2 gene in mouse

Dev Biol

(1993)

A Ghysen et al.

Cell interactions and gene interactions in peripheral neurogenesis

Genes Dev

(1993)

CR Coffman et al.

Expression of an extracellular deletion of Xotch diverts cell fate in Xenopus embryos

Cell

(1993)

JA Campos-Ortega

Mechanisms of early neurogenesis in Drosophila melanogaster

J Neurobiol

(1993)

D Srivastava et al.

A subclass of bHLH proteins required for cardiac morphogenesis

Science

(1995)

P Cserjesi et al.

Scleraxis: a basis helix-loop-helix protein that prefigures skeletal formation during mouse embryogenesis

Development

(1995)

CV Cabera et al.

Transcriptional activation by heterodimers of the achaete-scute and duaghterless gene products of Drosophila

EMBO J

(1991)

JE Johnson et al.

Two rat homologues of Drosophila achaete-scute specifically expressed in neuronal precursors

Nature

(1990)

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Basic helix-loop-helix genes in neural development

Abstract

Cell

Cell

Cell

Cell

Dev Biol

Dev Biol

Cell

Mech Dev

J Biol Chem

Mech Dev

Mol Cell Neurosci

Proc Natl Acad Sci USA

Science

Genes Dev

Dev Biol

Genes Dev

Cell

Mechanisms of early neurogenesis in Drosophila melanogaster

J Neurobiol

A subclass of bHLH proteins required for cardiac morphogenesis

Science

Scleraxis: a basis helix-loop-helix protein that prefigures skeletal formation during mouse embryogenesis

Development

Transcriptional activation by heterodimers of the achaete-scute and duaghterless gene products of Drosophila

EMBO J

Two rat homologues of Drosophila achaete-scute specifically expressed in neuronal precursors

Nature