Cell lineage determination and the control of neuronal identity in the neural crest (original) (raw)
Related papers
Mechanisms and perspectives on differentiation of autonomic neurons
Developmental Biology, 2005
Neurons share many features in common but are distinguished by expression of phenotypic characteristics that define their specific function, location, or connectivity. One aspect of neuronal fate determination that has been extensively studied is that of neurotransmitter choice. The generation of diversity of neuronal subtypes within the developing nervous system involves integration of extrinsic and intrinsic instructive cues resulting in the expression of a core set of regulatory molecules. This review focuses on mechanisms of growth and transcription factor regulation in the generation of peripheral neural crest-derived neurons. Although the specification and differentiation of noradrenergic neurons are the focus, I have tried to integrate these into a larger picture providing a general roadmap for development of autonomic neurons. There is a core of DNA binding proteins required for the development of sympathetic, parasympathetic, and enteric neurons, including Phox2 and MASH1, whose specificity is regulated by the recruitment of additional transcriptional regulators in a subtypespecific manner. For noradrenergic neurons, the basic helix-loop-helix DNA binding protein HAND2 (dHAND) appears to serve this function. The studies reviewed here support the notion that neurotransmitter identity is closely linked to other aspects of neurogenesis and reveal a molecular mechanism to coordinate expression of pan-neuronal genes with cell type-specific genes.
Deconstructing cell determination: proneural genes and neuronal identity
BioEssays, 1999
Vertebrates express scores of bHLH proteins during neural development. Earlier studies inspired by the established role of ''proneural'' genes in fly neurogenesis, as well as by the vertebrate bHLH myogenic program, focused on the reconstruction of bHLH gene cascades, which are thought to control successive steps leading to neuronal differentiation. Little attention has been paid thus far to the relationship between the diversity of neural bHLH genes and the diversity of neuronal phenotypes. This article reviews recent evidence that, akin to their fly counterparts, vertebrate neural bHLH genes probably confer not only ''generic'' neuronal properties, but also neuronal type-specific properties, inextricably linking neural determination and the specification of neuronal identity. We also speculate on the relations between positional information and gene activity, and on the evolutionary significance of the diversity of bHLH genes.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1997
Genetic studies in Drosophila and in vertebrates have implicated basic helix-loop-helix (bHLH) genes in neuronal fate determination and cell type specification. We have compared directly the expression of Mash1 and neurogenin1 (ngn1), two bHLH genes that are expressed specifically at early stages of neurogenesis. In the PNS these genes are expressed in complementary autonomic and sensory lineages. In the CNS in situ hybridization to serial sections and double-labeling experiments indicate that Mash1 and ngn1 are expressed in adjacent and nonoverlapping regions of the neuroepithelium that correspond to future functionally distinct areas of the brain. We also showed that in the PNS several other bHLH genes exhibit similar lineal restriction, as do ngn1 and Mash1, suggesting that complementary cascades of bHLH factors are involved in PNS development. Finally, we found that there is a close association between expression of ngn1 and Mash1 and that of two Notch ligands. These observation...
Crossregulation between Neurogenin2 and Pathways Specifying Neuronal Identity in the Spinal Cord
Neuron, 2001
subsequently by the floor plate (reviewed in . Shh acts in a concentration-dependent manner to both induce the expression of some homeodomain proteins (e.g., Nkx2.2 and Nkx6.1) and repress that of others (e.g., Pax6, Irx3, Dbx2). The expression of specific Raffaella Scardigli, Carol Schuurmans, Gé rard Gradwohl, and Franç ois Guillemot 1 Institut de Gé né tique et de Biologie Molé culaire et Cellulaire CNRS/INSERM/Université Louis Pasteur combinations of homeodomain proteins at different DV B.P. 163 levels of the neural tube results in the establishment of 67404 Illkirch Cé dex distinct progenitor domains which give rise to particular C.U. de Strasbourg classes of neurons. The function of these early ex-France pressed homeodomain proteins in specifying neuronal fates is thought to be relayed through the action of another set of homeodomain proteins that are ex-Summary pressed by progenitor cells as they exit the cell cycle and begin to differentiate (Briscoe et al., 2000; Jessell, We have examined how genetic pathways that specify 2000). Among these are MNR2 and Hb9, two related neuronal identity and regulate neurogenesis interface factors that have been implicated in the specification of in the vertebrate neural tube. Here, we demonstrate MN identity in chick (Tanabe et al., 1998) and in mouse that expression of the proneural gene Neurogenin2 (Arber et al., 1999; Thaler et al., 1999), and Lim3, which (Ngn2) in the ventral spinal cord results from the moduis involved in the specification of V2 interneurons and lar activity of three enhancers active in distinct progena subtype of MNs (Sharma et al., 1998). itor domains, suggesting that Ngn2 expression is con-Members of the basic helix-loop-helix (bHLH) class trolled by dorsoventral patterning signals. Consistent of transcription factors play essential roles in lineage with this hypothesis, Ngn2 enhancer activity is dependetermination and in the differentiation of neural progendent on the function of Pax6, a homeodomain facitors (Kageyama and Nakanishi, 1997; Guillemot, 1999). tor involved in specifying the identity of ventral spinal Pioneering studies in Drosophila have demonstrated cord progenitors. Moreover, we show that Ngn2 is rethat proneural genes of the achaete-scute complex and quired for the correct expression of Pax6 and several atonal confer neural competence to ectodermal cells homeodomain proteins expressed in defined neuronal and control the selection of individual neural precursors populations. Thus, neuronal differentiation involves from clusters of initially equivalent cells (Jan and Jan, crossregulatory interactions between a bHLH-driven 1994). Loss-and gain-of-function studies have provided program of neurogenesis and genetic pathways specievidence that vertebrate homologs of the fly proneural fying progenitor and neuronal identity in the spinal genes function in a similar manner. For example, the cord. murine achaete-scute homolog Mash1 is required for the generation of neural progenitors in the ventral fore-Introduction brain and olfactory epithelium (Cau et al., 1997; Casarosa et al., 1999). Similarly, the atonal-related genes Progenitor populations located in different regions of the Neurogenin1 (Ngn1) and Neurogenin2 (Ngn2) are reneural tube undergo distinct programs of neurogenesis, quired for the generation of progenitors of cranial sengiving rise to specific neuronal subtypes at precise desory ganglia (Fode et al., 1998; Ma et al., 1998), while velopmental times (McConnell, 1995). The molecular the atonal ortholog Math1 is required for the generation pathways that control the generation and differentiation of cerebellar granular cells (Ben-Arie et al., 1997). of neurons and the specification of their identity are In addition to these early functions in the determinastarting to be unraveled (Edlund and Jessell, 1999). It tion of neural lineages, proneural genes have been impliremains unclear, however, how these pathways are intecated in the specification of neuronal phenotypes in grated to yield the highly diverse and reproducible patboth Drosophila and vertebrates (Jan and Jan, 1994; terns of neuronal differentiation that characterize the Jarman and Ahmed, 1998; Brunet and Ghysen, 1999; developing neural tube (Tanabe and Jessell, 1996; An-Guillemot, 1999). In vertebrates, Mash1, Math1, and the derson and Jan, 1997). Ngns are expressed in largely nonoverlapping popula-The question of how different classes of neurons are tions of progenitor cells that give rise to different types generated at distinct positions in the nervous system of neurons. In the peripheral nervous system (PNS), has been best addressed in the ventral spinal cord Mash1 is expressed in progenitors of autonomic neu-(Briscoe et al., 2000). Motor neurons (MNs) and inrons where it controls the acquisition of a noradrenergic terneurons are derived from progenitor cell populations neurotransmission phenotype. This occurs through the located at defined positions along the dorsoventral (DV) regulation by Mash1 of the expression of Phox2a, a axis of the neural tube. The DV identity of progenitor homeodomain protein that controls noradrenergic difcells in the ventral spinal cord is specified in response ferentiation by directly regulating the expression of the to graded concentrations of Sonic hedgehog (Shh), a catecholamine biosynthetic enzymes tyrosine hydroxymorphogen that is secreted first by the notochord and lase and dopamine -hydroxylase (Lo et al., 1997; Hirsch et al., 1998; Goridis and Brunet, 1999). Expression of the Ngns in the PNS is complementary to that of Mash1 1 Correspondence: francois@igbmc.u-strasbg.fr Neuron 204
PloS Genetics, 2016
During central nervous system (CNS) development neural stem cells (Neuroblasts, NBs) have to acquire an identity appropriate to their location. In thoracic and abdominal segments of Drosophila, the expression pattern of Bithorax-Complex Hox genes is known to specify the segmental identity of NBs prior to their delamination from the neuroectoderm. Compared to the thoracic, ground state segmental units in the head region are derived to different degrees, and the precise mechanism of segmental specification of NBs in this region is still unclear. We identified and characterized a set of serially homologous NB-lineages in the gnathal segments and used one of them (NB6-4 lineage) as a model to investigate the mechanism conferring segment-specific identities to gnathal NBs. We show that NB6-4 is primarily determined by the cell-autonomous function of the Hox gene Deformed (Dfd). Interestingly, however, it also requires a non-cell-autonomous function of labial and Anten-napedia that are expressed in adjacent anterior or posterior compartments. We identify the secreted molecule Amalgam (Ama) as a downstream target of the Antennapedia-Complex Hox genes labial, Dfd, Sex combs reduced and Antennapedia. In conjunction with its receptor Neurotactin (Nrt) and the effector kinase Abelson tyrosine kinase (Abl), Ama is necessary in parallel to the cell-autonomous Dfd pathway for the correct specification of the maxillary identity of NB6-4. Both pathways repress CyclinE (CycE) and loss of function of either of these pathways leads to a partial transformation (40%), whereas simultaneous mutation of both pathways leads to a complete transformation (100%) of NB6-4 segmental identity. Finally, we provide genetic evidences, that the Ama-Nrt-Abl-pathway regulates CycE expression by altering the function of the Hippo effector Yorkie in embryonic NBs. The disclosure of a non-cell-autonomous influence of Hox genes on neural stem cells provides new insight into the process of segmental patterning in the developing CNS.
Human Molecular Genetics, 1996
atonal is a Drosophila proneural gene that belongs to the family of basic helix-loop-helix (bHLH)-containing proteins. It is expressed in the chordotonal organs and photoreceptor cells, and flies that lack Atonal protein are ataxic and blind. Here we report the cloning of atonal homologs from red flour beetle, puffer fish, chicken, mouse, and human. The bHLH domain is conserved throughout evolution, while the entire coding region is highly similar in mammals. Both the chicken and the mouse homologs are expressed early in embryogenesis in the hind brain, and specifically in cells predicted to give rise to the external granular layer of the cerebellum. In addition, these genes are expressed throughout the dorsal part of the spinal cord, in patterns different from those found for other genes, like LH-2 and wnt-1. The mouse homolog (Math1) maps to mouse chromosome 6, and the human homolog (HATH1) to human chromosome 4q22. Two neurological mouse mutants, Lc and chp, were found to map to the vicinity of Math1, but are not caused by mutations in Math1. The evolutionary conservation of this gene and its mRNA expression patterns during embryogenesis suggests that it plays a key role in the development of the vertebrate central nervous system.
Molecular and Cellular Neuroscience, 1996
We recently identified neurogenin (ngn), a neuroD-related bHLH gene, whose Xenopus homolog functions as a neuronal determination factor and upstream activator of XneuroD (Ma et al. Cell 87: 43-52, 1996). Here we identify two additional ngn's, ngn2 and ngn3, which together define a novel subfamily of atonal-related mouse genes. Comparative analysis of ngn expression indicates that these three genes define distinct progenitor populations in the developing CNS and PNS, exhibiting nonoverlapping expression in some areas and partial overlap in others. The expression of the ngn's spatially overlaps and often temporally precedes that of neuroD, suggesting that (as in Xenopus) the ngn's and neuroD function in a cascade. Thus, as in myogenesis, different bHLH determination factors may activate a common bHLH differentiation factor in different sublineages. The ngn's therefore represent both a family of putative mammalian neuronal determination genes and useful markers of the origins of neuronal diversity.
Development, 2009
The Olig3 gene encodes a bHLH factor that is expressed in the ventricular zone of the dorsal alar plate of the hindbrain. We found that the Olig3 + progenitor domain encompassed subdomains that co-expressed Math1, Ngn1, Mash1 and Ptf1a. Olig3 + cells give rise to neuronal types in the dorsal alar plate that we denote as class A neurons. We used genetic lineage tracing to demonstrate that class A neurons contribute to the nucleus of the solitary tract and to precerebellar nuclei. The fate of class A neurons was not correctly determined in Olig3 mutant mice. As a consequence, the nucleus of the solitary tract did not form, and precerebellar nuclei, such as the inferior olivary nucleus, were absent or small. At the expense of class A neurons, ectopic Lbx1 + neurons appeared in the alar plate in Olig3 mutant mice. By contrast, electroporation of an Olig3 expression vector in the chick hindbrain suppressed the emergence of Lbx1 + neurons. Climbing fiber neurons of the inferior olivary nucleus express Foxd3 and require Olig3 as well as Ptf1a for the determination of their fate. We observed that electroporation of Olig3 and Ptf1a expression vectors, but not either alone, induced Foxd3. We therefore propose that Olig3 can cooperate with Ptf1a to determine the fate of climbing fiber neurons of the inferior olivary nucleus.