The C. elegans NeuroD homolog cnd-1 functions in multiple aspects of motor neuron fate specification.

The basic helix-loop-helix transcription factor NeuroD (Neurod1) has been implicated in neuronal fate determination, differentiation and survival. Here we report the expression and functional analysis of cnd-1, a C. elegans NeuroD homolog. cnd-1 expression was first detected in neuroblasts of the AB lineage in 14 cell embryos and maintained in many neuronal descendants of the AB lineage during embryogenesis, diminishing in most terminally differentiated neurons prior to hatching. Specifically, cnd-1 reporter genes were expressed in the precursors of the embryonic ventral cord motor neurons and their progeny. A loss-of-function mutant, cnd-1(ju29), exhibited multiple defects in the ventral cord motor neurons. First, the number of motor neurons was reduced, possibly caused by the premature withdrawal of the precursors from mitotic cycles. Second, the strict correlation between the fate of a motor neuron with respect to its lineage and position in the ventral cord was disrupted, as manifested by the variable expression pattern of motor neuron fate specific markers. Third, motor neurons also exhibited defects in terminal differentiation characteristics including axonal morphology and synaptic connectivity. Finally, the expression patterns of three neuronal type-specific transcription factors, unc-3, unc-4 and unc-30, were altered. Our data suggest that cnd-1 may specify the identity of ventral cord motor neurons both by maintaining the mitotic competence of their precursors and by modulating the expression of neuronal type-specific determination factors. cnd-1 appears to have combined the functions of several vertebrate neurogenic bHLH proteins and may represent an ancestral form of this protein family.

[1]  C. Chien,et al.  The Proneural Gene amos Promotes Multiple Dendritic Neuron Formation in the Drosophila Peripheral Nervous System , 2000, Neuron.

[2]  A. Jarman,et al.  amos, a Proneural Gene for Drosophila Olfactory Sense Organs that Is Regulated by lozenge , 2000, Neuron.

[3]  K. Wallace,et al.  The pan‐neural bHLH proteins DEADPAN and ASENSE regulate mitotic activity and cdk inhibitor dacapo expression in the Drosophila larval optic lobes , 2000, Genesis.

[4]  F. Guillemot.  Vertebrate bHLH genes and the determination of neuronal fates. , 1999, Experimental cell research.

[5]  I. Morano,et al.  Remodeling of the hypertrophied human myocardium by cardiac bHLH transcription factors , 1999, Journal of cellular biochemistry.

[6]  H. Horvitz,et al.  Coordinated Transcriptional Regulation of the unc-25Glutamic Acid Decarboxylase and the unc-47 GABA Vesicular Transporter by the Caenorhabditis elegans UNC-30 Homeodomain Protein , 1999, The Journal of Neuroscience.

[7]  T. Miyata,et al.  NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus. , 1999, Genes & development.

[8]  F. Guillemot,et al.  Neurogenin1 and neurogenin2 control two distinct waves of neurogenesis in developing dorsal root ganglia. , 1999, Genes & development.

[9]  K. Tomita,et al.  The bHLH gene Hes1 is essential for expansion of early T cell precursors. , 1999, Genes & development.

[10]  D. O'Leary,et al.  Defects in thalamocortical axon pathfinding correlate with altered cell domains in Mash-1-deficient mice. , 1999, Development.

[11]  A. Fire,et al.  Two-color GFP expression system for C. elegans. , 1999, BioTechniques.

[12]  A. Ghysen,et al.  Deconstructing cell determination: proneural genes and neuronal identity , 1999, BioEssays : news and reviews in molecular, cellular and developmental biology.

[13]  C. Goridis,et al.  Transcriptional control of neurotransmitter phenotype , 1999, Current Opinion in Neurobiology.

[14]  A. Chitnis.  Control of neurogenesis — lessons from frogs, fish and flies , 1999, Current Opinion in Neurobiology.

[15]  T. Jessell,et al.  Progression from Extrinsic to Intrinsic Signaling in Cell Fate Specification A View from the Nervous System , 1999, Cell.

[16]  H. Horvitz,et al.  The Caenorhabditis elegans Gene unc-25Encodes Glutamic Acid Decarboxylase and Is Required for Synaptic Transmission But Not Synaptic Development , 1999, The Journal of Neuroscience.

[17]  S. Hallam,et al.  lin-14 regulates the timing of synaptic remodelling in Caenorhabditis elegans , 1998, Nature.

[18]  B. Göttgens,et al.  The SCL gene specifies haemangioblast development from early mesoderm , 1998, The EMBO journal.

[19]  C. Lanctôt,et al.  The PTX family of homeodomain transcription factors during pituitary developments , 1998, Molecular and Cellular Endocrinology.

[20]  B. Ye,et al.  unc-3, a gene required for axonal guidance in Caenorhabditis elegans, encodes a member of the O/E family of transcription factors. , 1998, Development.

[21]  D. Srivastava,et al.  The bHLH factors, dHAND and eHAND, specify pulmonary and systemic cardiac ventricles independent of left-right sidedness. , 1998, Developmental biology.

[22]  J. Johnson,et al.  Progenitors of dorsal commissural interneurons are defined by MATH1 expression. , 1998, Development.

[23]  F. Guillemot,et al.  The bHLH Protein NEUROGENIN 2 Is a Determination Factor for Epibranchial Placode–Derived Sensory Neurons , 1998, Neuron.

[24]  A. Ghysen,et al.  Expression and function of tap in the gustatory and olfactory organs of Drosophila. , 1998, The International journal of developmental biology.

[25]  David J. Anderson,et al.  neurogenin1 Is Essential for the Determination of Neuronal Precursors for Proximal Cranial Sensory Ganglia , 1998, Neuron.

[26]  D. Anderson,et al.  MASH1 activates expression of the paired homeodomain transcription factor Phox2a, and couples pan-neuronal and subtype-specific components of autonomic neuronal identity. , 1998, Development.

[27]  K. Tomita,et al.  bHLH transcription factors and mammalian neuronal differentiation. , 1997, The international journal of biochemistry & cell biology.

[28]  H. Zoghbi,et al.  Math1 is essential for genesis of cerebellar granule neurons , 1997, Nature.

[29]  A. Fire,et al.  A C. elegans E/Daughterless bHLH protein marks neuronal but not striated muscle development. , 1997, Development.

[30]  R. Y. Tsai,et al.  Cloning and Functional Characterization of Roaz, a Zinc Finger Protein that Interacts with O/E-1 to Regulate Gene Expression: Implications for Olfactory Neuronal Development , 1997, The Journal of Neuroscience.

[31]  A. Ghysen,et al.  tap, a Drosophila bHLH gene expressed in chemosensory organs. , 1997, Gene.

[32]  F. Guillemot,et al.  Mash1 activates a cascade of bHLH regulators in olfactory neuron progenitors. , 1997, Development.

[33]  S. Tapscott,et al.  Two domains of MyoD mediate transcriptional activation of genes in repressive chromatin: a mechanism for lineage determination in myogenesis. , 1997, Genes & development.

[34]  Jacqueline E. Lee.  Basic helix-loop-helix genes in neural development , 1997, Current Opinion in Neurobiology.

[35]  M. Cole,et al.  Biparous: a novel bHLH gene expressed in neuronal and glial precursors in Drosophila. , 1996, Developmental biology.

[36]  D. Anderson,et al.  Identification of novel paired homeodomain protein related to C. elegans unc-4 as a potential downstream target of MASH1. , 1996, Developmental biology.

[37]  David J. Anderson,et al.  Identification of neurogenin, a Vertebrate Neuronal Determination Gene , 1996, Cell.

[38]  David J. Anderson,et al.  neurogenins,a Novel Family ofatonal-Related bHLH Transcription Factors, Are Putative Mammalian Neuronal Determination Genes That Reveal Progenitor Cell Heterogeneity in the Developing CNS and PNS , 1996, Molecular and Cellular Neuroscience.

[39]  H. Horvitz,et al.  The Caenorhabditis elegans LIN-26 protein is required to specify and/or maintain all non-neuronal ectodermal cell fates. , 1996, Development.

[40]  A. Chitnis,et al.  Sensitivity of proneural genes to lateral inhibition affects the pattern of primary neurons in Xenopus embryos. , 1996, Development.

[41]  D. Srivastava,et al.  A Subclass of bHLH Proteins Required for Cardiac Morphogenesis , 1995, Science.

[42]  D M Miller,et al.  Expression of the unc-4 homeoprotein in Caenorhabditis elegans motor neurons specifies presynaptic input. , 1995, Development.

[43]  H. Weintraub,et al.  Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein. , 1995, Science.

[44]  G. Hannon,et al.  Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD , 1995, Science.

[45]  Scott W. Emmons,et al.  A transcription factor controlling development of peripheral sense organs in C. elegans , 1995, Nature.

[46]  Yishi Jin,et al.  Control of type-D GABAergic neuron differentiation by C. elegans UNC-30 homeodomain protein , 1994, Nature.

[47]  S. Bray,et al.  The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo. , 1994, Development.

[48]  H. Horvitz,et al.  The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins. , 1994, Genetics.

[49]  Yuh Nung Jan,et al.  atonal is the proneural gene for Drosophila photoreceptors , 1994, Nature.

[50]  J. Campos-Ortega,et al.  The basic-helix-loop-helix domain of Drosophila lethal of scute protein is sufficient for proneural function and activates neurogenic genes , 1994, Cell.

[51]  Shai Shaham,et al.  The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme , 1993, Cell.

[52]  David J. Anderson,et al.  Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons , 1993, Cell.

[53]  Y. Jan,et al.  asense is a Drosophila neural precursor gene and is capable of initiating sense organ formation. , 1993, Development.

[54]  A. Joyner,et al.  Dynamic expression of the murine Achaete-Scute homologue Mash-1 in the developing nervous system , 1993, Mechanisms of Development.

[55]  Yves Grau,et al.  atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system , 1993, Cell.

[56]  Gary Ruvkun,et al.  C. elegans unc-4 gene encodes a homeodomain protein that determines the pattern of synaptic input to specific motor neurons , 1992, Nature.

[57]  H. Horvitz,et al.  Genes necessary for directed axonal elongation or fasciculation in C. elegans , 1992, Neuron.

[58]  V. Ambros,et al.  Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. , 1991, The EMBO journal.

[59]  T. Saito,et al.  Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells. , 1991, Genes & development.

[60]  Gary Ruvkun,et al.  The unc-86 gene product couples cell lineage and cell identity in C. elegans , 1990, Cell.

[61]  P. Simpson,et al.  Lateral inhibition and the development of the sensory bristles of the adult peripheral nervous system of Drosophila. , 1990, Development.

[62]  Y. Jan,et al.  Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence , 1989, Cell.

[63]  N. Munakata.  [Genetics of Caenorhabditis elegans]. , 1989, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[64]  A. Ghysen,et al.  From DNA to form: the achaete-scute complex. , 1988, Genes & development.

[65]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[66]  J. Sulston,et al.  The embryonic cell lineage of the nematode Caenorhabditis elegans. , 1983, Developmental biology.

[67]  D. Albertson,et al.  Connectivity changes in a class of motoneurone during the development of a nematode , 1978, Nature.

[68]  J. Sulston,et al.  Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. , 1977, Developmental biology.

[69]  David J. Anderson,et al.  NEUROGENIN 1 and NEUROGENIN 2 control two distinct waves of neurogenesis in developing dorsal root ganglia , 1999 .

[70]  C. Cepko,et al.  NeuroD regulates multiple functions in the developing neural retina in rodent. , 1999, Development.

[71]  J. Campos-Ortega.  The genetics of the Drosophila achaete-scute gene complex: a historical appraisal. , 1998, The International journal of developmental biology.

[72]  Y. Jan,et al.  Genetic control of cell fate specification in Drosophila peripheral nervous system. , 1994, Annual review of genetics.