Genomes and Genes
Gene Symbol: Nkx2-2
Description: NK2 homeobox 2
Alias: Nkx-2.2, Nkx2.2, tinman, homeobox protein Nkx-2.2, Drosophila NK2 transcription factor related, locus 2, NK2 transcription factor related, locus 2, glycoprotein GP330, renal, homeobox protein NK-2 homolog B, homeobox protein Nkx2-2
- Briscoe J, Pierani A, Jessell T, Ericson J. A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell. 2000;101:435-45 pubmed..The combinatorial expression of three of these proteins--Nkx6.1, Nkx2.2, and Irx3--specifies the identity of three classes of neurons generated in the ventral third of the neural tube. ..
- Prado C, Pugh Bernard A, Elghazi L, Sosa Pineda B, Sussel L. Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. Proc Natl Acad Sci U S A. 2004;101:2924-9 pubmed..2 and Pax4 are required to specify or maintain differentiation of the beta cell fate. This finding also suggests that there is a genetic component underlying the balance between insulin and ghrelin in regulating glucose metabolism. ..
- Peltopuro P, Kala K, Partanen J. Distinct requirements for Ascl1 in subpopulations of midbrain GABAergic neurons. Dev Biol. 2010;343:63-70 pubmed publisher..Also, our results have implications on understanding the origins of the various midbrain GABAergic neuron groups in the embryonic neuroepithelium. ..
- Huangfu D, Anderson K. Cilia and Hedgehog responsiveness in the mouse. Proc Natl Acad Sci U S A. 2005;102:11325-30 pubmed
- Sun T, Echelard Y, Lu R, Yuk D, Kaing S, Stiles C, et al. Olig bHLH proteins interact with homeodomain proteins to regulate cell fate acquisition in progenitors of the ventral neural tube. Curr Biol. 2001;11:1413-20 pubmed..In particular, interactions between Olig and Nkx2.2 proteins inhibit V3 interneuron development and promote the formation of alternate cell types, including those expressing Sox10. ..
- Desai S, Loomis Z, Pugh Bernard A, Schrunk J, Doyle M, Minic A, et al. Nkx2.2 regulates cell fate choice in the enteroendocrine cell lineages of the intestine. Dev Biol. 2008;313:58-66 pubmed..2 in intestinal endocrine cell development and reveal the regulatory similarities between cell type specification in the pancreatic islet and in the enteroendocrine population of the intestine. ..
- Sander M, Sussel L, Conners J, Scheel D, Kalamaras J, Dela Cruz F, et al. Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas. Development. 2000;127:5533-40 pubmed..Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation. ..
- Nakatani T, Minaki Y, Kumai M, Ono Y. Helt determines GABAergic over glutamatergic neuronal fate by repressing Ngn genes in the developing mesencephalon. Development. 2007;134:2783-93 pubmed
- Cortellino S, Wang C, Wang B, Bassi M, Caretti E, Champeval D, et al. Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4. Dev Biol. 2009;325:225-37 pubmed publisher..We conclude that complex A and complex B factors play similar but distinct roles in ciliogenesis and Shh/Gli3 signaling. ..
- Jeong J, McMahon A. Growth and pattern of the mammalian neural tube are governed by partially overlapping feedback activities of the hedgehog antagonists patched 1 and Hhip1. Development. 2005;132:143-54 pubmed..Furthermore, this feedback mechanism is crucial in generating a neural tube that contains appropriate numbers of all ventral and intermediate neuronal cell types. ..
- Ribes V, Balaskas N, Sasai N, Cruz C, Dessaud E, Cayuso J, et al. Distinct Sonic Hedgehog signaling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube. Genes Dev. 2010;24:1186-200 pubmed publisher..In addition, we provide evidence supporting a common scheme for FP specification by Shh signaling that reconciles mechanisms of FP development in teleosts and amniotes. ..
- Sun T, Dong H, Wu L, Kane M, Rowitch D, Stiles C. Cross-repressive interaction of the Olig2 and Nkx2.2 transcription factors in developing neural tube associated with formation of a specific physical complex. J Neurosci. 2003;23:9547-56 pubmed..2 that helps to establish the pMN-p3 boundary in the developing spinal cord. ..
- Ohta Y, Kosaka Y, Kishimoto N, Wang J, Smith S, Honig G, et al. Convergence of the insulin and serotonin programs in the pancreatic ?-cell. Diabetes. 2011;60:3208-16 pubmed publisher..The interrelated biology of these two cell types has important implications for the pathology and treatment of diabetes. ..
- Artner I, Blanchi B, Raum J, Guo M, Kaneko T, Cordes S, et al. MafB is required for islet beta cell maturation. Proc Natl Acad Sci U S A. 2007;104:3853-8 pubmed..These results demonstrate that MafB plays a previously uncharacterized role by regulating transcription of key factors during development that are required for the production of mature alpha and beta cells. ..
- CHAO C, Loomis Z, Lee J, Sussel L. Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells. Dev Biol. 2007;312:523-32 pubmed..Furthermore, this study reveals a previously unappreciated early function of NeuroD1 in regulating the specification of alpha, PP and epsilon cells. ..
- Du A, McCracken K, Walp E, Terry N, Klein T, Han A, et al. Arx is required for normal enteroendocrine cell development in mice and humans. Dev Biol. 2012;365:175-88 pubmed publisher..Taken together, our findings uncover a novel and conserved role of Arx in mammalian endocrine cell development and provide a potential cause for the chronic diarrhea seen in both humans and mice carrying Arx mutations. ..
- Tang M, Miyamoto Y, Huang E. Multiple roles of beta-catenin in controlling the neurogenic niche for midbrain dopamine neurons. Development. 2009;136:2027-38 pubmed publisher..They also suggest that beta-catenin-mediated signaling pathways can be targeted to promote and expand DA neurons in cell-based therapeutic strategies. ..
- Matise M, Epstein D, Park H, Platt K, Joyner A. Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system. Development. 1998;125:2759-70 pubmed
- Gao N, LeLay J, Vatamaniuk M, Rieck S, Friedman J, Kaestner K. Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development. Genes Dev. 2008;22:3435-48 pubmed publisher..Thus, the regulation of Pdx1 expression by Foxa1 and Foxa2 is a key early event controlling the expansion and differentiation of the pancreatic primordia. ..
- Bangs F, Antonio N, Thongnuek P, Welten M, Davey M, Briscoe J, et al. Generation of mice with functional inactivation of talpid3, a gene first identified in chicken. Development. 2011;138:3261-72 pubmed publisher..This genetic mouse model will facilitate further conditional approaches, epistatic experiments and open up investigation into the function of the novel talpid3 gene using the many resources available for mice. ..
- Seymour P, Freude K, Tran M, Mayes E, Jensen J, Kist R, et al. SOX9 is required for maintenance of the pancreatic progenitor cell pool. Proc Natl Acad Sci U S A. 2007;104:1865-70 pubmed..These findings will be of major significance for the development of in vitro protocols for cell replacement therapies. ..
- Persson M, Stamataki D, te Welscher P, Andersson E, Böse J, Ruther U, et al. Dorsal-ventral patterning of the spinal cord requires Gli3 transcriptional repressor activity. Genes Dev. 2002;16:2865-78 pubmed..Together these data raise the possibility that Gli proteins act as common mediators integrating Shh signals, and other sources of positional information, to control patterning throughout the ventral neural tube. ..
- Wang H, Lei Q, Oosterveen T, Ericson J, Matise M. Tcf/Lef repressors differentially regulate Shh-Gli target gene activation thresholds to generate progenitor patterning in the developing CNS. Development. 2011;138:3711-21 pubmed publisher..Together, our data reveal a Shh-Gli-independent transcriptional input that is required to shape the precise spatial and temporal response to extracellular morphogen signaling information during lineage segregation in the CNS. ..
- Bai C, Joyner A. Gli1 can rescue the in vivo function of Gli2. Development. 2001;128:5161-72 pubmed..We show that the defects are enhanced when Gli3 function is reduced, demonstrating that an important difference between Gli1 and Gli2 is the ability of Gli1 to antagonize Gli3 function. ..
- Raum J, Gerrish K, Artner I, Henderson E, Guo M, Sussel L, et al. FoxA2, Nkx2.2, and PDX-1 regulate islet beta-cell-specific mafA expression through conserved sequences located between base pairs -8118 and -7750 upstream from the transcription start site. Mol Cell Biol. 2006;26:5735-43 pubmed..2 null animals. These results suggest that beta-cell-type-specific mafA transcription is principally controlled by region 3-acting transcription factors that are essential in the formation of functional beta cells. ..
- Huang Y, Roelink H, McKnight G. Protein kinase A deficiency causes axially localized neural tube defects in mice. J Biol Chem. 2002;277:19889-96 pubmed..The regional sensitivity to changes in PKA activity indicates that downstream signaling pathways differ along the anterior-posterior axis and suggests a functional role for PKA activation in neural tube development. ..
- Papizan J, Singer R, Tschen S, Dhawan S, Friel J, Hipkens S, et al. Nkx2.2 repressor complex regulates islet ?-cell specification and prevents ?-to-?-cell reprogramming. Genes Dev. 2011;25:2291-305 pubmed publisher..Mutation of the endogenous Nkx2.2 tinman (TN) domain in mice abolishes the interaction between Nkx2.2 and Grg3 and disrupts ?-cell specification...
- Eggenschwiler J, Espinoza E, Anderson K. Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway. Nature. 2001;412:194-8 pubmed..The data indicate that dorsalizing signals activate transcription of Rab23 in order to silence the Shh pathway in dorsal neural cells. ..
- Doyle M, Loomis Z, Sussel L. Nkx2.2-repressor activity is sufficient to specify alpha-cells and a small number of beta-cells in the pancreatic islet. Development. 2007;134:515-23 pubmed..2 through its TN domain. These studies suggest that Nkx2.2 functions predominantly as a transcriptional repressor during specification of endocrine cell types in the pancreas. ..
- Sun T, Pringle N, Hardy A, Richardson W, Smith H. Pax6 influences the time and site of origin of glial precursors in the ventral neural tube. Mol Cell Neurosci. 1998;12:228-39 pubmed..OLs developed normally in explants of Isl1(-/-) spinal cords, which lack MNs, arguing against feedback control and suggesting that the neuron-glia switch is an intrinsic developmental program in a specific subset of neural precursors. ..
- Scardigli R, Schuurmans C, Gradwohl G, Guillemot F. Crossregulation between Neurogenin2 and pathways specifying neuronal identity in the spinal cord. Neuron. 2001;31:203-17 pubmed..Thus, neuronal differentiation involves crossregulatory interactions between a bHLH-driven program of neurogenesis and genetic pathways specifying progenitor and neuronal identity in the spinal cord. ..
- Lu Q, Yuk D, Alberta J, Zhu Z, Pawlitzky I, Chan J, et al. Sonic hedgehog--regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron. 2000;25:317-29 pubmed..Gain- and loss-of-function analyses in transgenic mice demonstrate that Shh is both necessary and sufficient for Olg gene expression in vivo. ..
- Briscoe J, Sussel L, Serup P, HARTIGAN O CONNOR D, Jessell T, Rubenstein J, et al. Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature. 1999;398:622-7 pubmed..Thus, Nkx2.2 has an essential role in interpreting graded Shh signals and selecting neuronal identity. ..
- Okada A, Charron F, Morin S, Shin D, Wong K, Fabre P, et al. Boc is a receptor for sonic hedgehog in the guidance of commissural axons. Nature. 2006;444:369-73 pubmed..Taken together, these data suggest that Boc is essential as a receptor for Shh in commissural axon guidance. ..
- Doyle M, Sussel L. Nkx2.2 regulates beta-cell function in the mature islet. Diabetes. 2007;56:1999-2007 pubmed..2-repressor transgenic mice is associated with disrupted islet architecture. These studies indicate a previously undiscovered role for Nkx2.2 in the maintenance of mature beta-cell function and the formation of normal islet structure. ..
- Tang M, Villaescusa J, Luo S, Guitarte C, Lei S, Miyamoto Y, et al. Interactions of Wnt/beta-catenin signaling and sonic hedgehog regulate the neurogenesis of ventral midbrain dopamine neurons. J Neurosci. 2010;30:9280-91 pubmed publisher..Persistent activation of beta-catenin in early progenitors perturbs their cell cycle progression and antagonizes Shh expression, whereas activation of beta-catenin in midline progenitors promotes the generation of dopamine neurons. ..
- Vokes S, Ji H, McCuine S, Tenzen T, Giles S, Zhong S, et al. Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning. Development. 2007;134:1977-89 pubmed..Together, these approaches provide significant new insights into both tissue-specific and general transcriptional targets in a crucial Shh-mediated patterning process. ..
- Ding Y, Marklund U, Yuan W, Yin J, Wegman L, Ericson J, et al. Lmx1b is essential for the development of serotonergic neurons. Nat Neurosci. 2003;6:933-8 pubmed..Moreover, our data indicate that genetic cascades controlling the caudal and rostral 5-HT neurons are distinct, despite their shared components. ..
- Pattyn A, Vallstedt A, Dias J, Samad O, Krumlauf R, Rijli F, et al. Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors. Genes Dev. 2003;17:729-37 pubmed..These findings assign new roles for Nkx, Hox, and Phox2 proteins in the control of temporal neuronal fate determination, and link spatial and temporal patterning of CNS neuronal fates. ..
- Takebayashi H, Ohtsuki T, Uchida T, Kawamoto S, Okubo K, Ikenaka K, et al. Non-overlapping expression of Olig3 and Olig2 in the embryonic neural tube. Mech Dev. 2002;113:169-74 pubmed..5. Olig3 is specifically and transiently expressed in different types of progenitors of embryonic central nervous system and then disappears in the course of development. ..
- Craven S, Lim K, Ye W, Engel J, de Sauvage F, Rosenthal A. Gata2 specifies serotonergic neurons downstream of sonic hedgehog. Development. 2004;131:1165-73 pubmed..Our findings reveal that the identity of closely related 5-HT subclasses occurs through distinct responses of adjacent rostrocaudal progenitor domains to broad ventral inducers. ..
- Lu Q, Sun T, Zhu Z, Ma N, Garcia M, Stiles C, et al. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell. 2002;109:75-86 pubmed..Neither Olig gene is required for astrocytes. These findings, together with fate mapping analysis of Olig-expressing cells, indicate that oligodendrocytes are derived from Olig-specified progenitors that give rise also to neurons. ..
- Keady B, Samtani R, Tobita K, Tsuchya M, San Agustin J, Follit J, et al. IFT25 links the signal-dependent movement of Hedgehog components to intraflagellar transport. Dev Cell. 2012;22:940-51 pubmed publisher..Thus, IFT function is not restricted to building cilia where signaling occurs, but also plays a separable role in signal transduction events. ..
- Honig G, Liou A, Berger M, German M, Tecott L. Precise pattern of recombination in serotonergic and hypothalamic neurons in a Pdx1-cre transgenic mouse line. J Biomed Sci. 2010;17:82 pubmed publisher..These results suggest that investigators employing this mouse line for studies of pancreatic function should consider the possible contributions of central nervous system effects towards resulting phenotypes. ..
- Balaskas N, Ribeiro A, Panovska J, Dessaud E, Sasai N, Page K, et al. Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube. Cell. 2012;148:273-84 pubmed publisher..Our findings reveal that morphogen interpretation is an emergent property of the architecture of a transcriptional network that provides robustness and reliability to tissue patterning. ..
- Jensen P, Farago A, Awatramani R, Scott M, Deneris E, Dymecki S. Redefining the serotonergic system by genetic lineage. Nat Neurosci. 2008;11:417-9 pubmed publisher..We uncovered a molecular framework for the serotonergic system that, having genetic lineages as its basis, is likely to have physiological relevance and will permit access to genetically defined subtypes for manipulation. ..
- Tran P, Haycraft C, Besschetnova T, Turbe Doan A, Stottmann R, Herron B, et al. THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet. 2008;40:403-410 pubmed publisher..Specifically, the aln mutation uncouples the roles of anterograde and retrograde transport in SHH signaling, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event. ..
- Decker K, Goldman D, Grasch C, Sussel L. Gata6 is an important regulator of mouse pancreas development. Dev Biol. 2006;298:415-29 pubmed..Conversely, the majority of transgenic Gata4-Engrailed embryos do not have a pancreatic phenotype. This study suggests that Gata6 is an important regulator of pancreas specification. ..
- Bulgakov O, Eggenschwiler J, Hong D, Anderson K, Li T. FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues. Development. 2004;131:2149-59 pubmed..Although it is expressed broadly, FKBP8 is required to antagonize SHH signaling primarily in neural tissues, suggesting that hedgehog signal transduction is subject to cell-type specific modulation during mammalian development. ..
- Holz A, Kollmus H, Ryge J, Niederkofler V, Dias J, Ericson J, et al. The transcription factors Nkx2.2 and Nkx2.9 play a novel role in floor plate development and commissural axon guidance. Development. 2010;137:4249-60 pubmed publisher..As both factors affect floor plate development, control of commissural axon trajectories might be the underlying mechanism. ..
- Li H, de Faria J, Andrew P, Nitarska J, Richardson W. Phosphorylation regulates OLIG2 cofactor choice and the motor neuron-oligodendrocyte fate switch. Neuron. 2011;69:918-29 pubmed publisher..Wild-type OLIG2 forms stable homodimers, whereas mutant (unphosphorylated) OLIG2(S147A) prefers to form heterodimers with Neurogenin 2 or other bHLH partners, suggesting a molecular basis for the switch. ..
- Park H, Bai C, Platt K, Matise M, Beeghly A, Hui C, et al. Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation. Development. 2000;127:1593-605 pubmed..Furthermore, Gli1 and Gli2, but not Gli1 and Gli3, have extensive overlapping functions that are likely downstream of SHH signaling. ..
- Arber S, Han B, Mendelsohn M, Smith M, Jessell T, Sockanathan S. Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron. 1999;23:659-74 pubmed..These findings show that HB9 has an essential function in consolidating the identity of postmitotic MNs. ..
- Vallstedt A, Klos J, Ericson J. Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain. Neuron. 2005;45:55-67 pubmed..Based on these findings, we propose that oligodendrocytes derive from several distinct positional origins and that the activation of Olig1/2 at different positions is controlled by distinct genetic programs. ..
- Perez Balaguer A, Puelles E, Wurst W, Martinez S. Shh dependent and independent maintenance of basal midbrain. Mech Dev. 2009;126:301-13 pubmed publisher..Based on our results and recently published data, we suggest the existence of a specific genetic pathway for the specification of the mesencephalic red nucleus. Foxa2 could be the candidate gene that might control this genetic pathway. ..
- Cissell M, Zhao L, Sussel L, Henderson E, Stein R. Transcription factor occupancy of the insulin gene in vivo. Evidence for direct regulation by Nkx2.2. J Biol Chem. 2003;278:751-6 pubmed..These studies reveal the broad application of the Pdx-1, BETA-2, Pax6, and Nkx2.2 transcription factors in regulating expression of genes selectively expressed in islet beta cells. ..
- Sussel L, Kalamaras J, Hartigan O Connor D, Meneses J, Pedersen R, Rubenstein J, et al. Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells. Development. 1998;125:2213-21 pubmed..1. We propose that Nkx2.2 is required for the final differentiation of pancreatic beta cells, and in its absence, beta cells are trapped in an incompletely differentiated state. ..
- Wang J, Elghazi L, Parker S, Kizilocak H, Asano M, Sussel L, et al. The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic beta-cell differentiation. Dev Biol. 2004;266:178-89 pubmed..This role of Pax4 appears to be accomplished via its genetic interaction with another homeobox gene, Nkx2.2. ..
- Bai C, Stephen D, Joyner A. All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3. Dev Cell. 2004;6:103-15 pubmed..Therefore, in the spinal cord all Hh signaling is Gli dependent. Furthermore, a combination of Gli2 and Gli3 is required to regulate motor neuron development and spatial patterning of ventral spinal cord progenitors. ..
- Kordowich S, Collombat P, Mansouri A, Serup P. Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage. BMC Dev Biol. 2011;11:52 pubmed publisher..Our analysis also suggests that one of the coupled functions of Nkx2.2 and Pax4 is to counteract Arx gene activity in early committed beta-cells. ..
- Ferri A, Lin W, Mavromatakis Y, Wang J, Sasaki H, Whitsett J, et al. Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner. Development. 2007;134:2761-9 pubmed..Altogether, our results demonstrate that Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner. ..
- Bai C, Auerbach W, Lee J, Stephen D, Joyner A. Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway. Development. 2002;129:4753-61 pubmed..Our studies demonstrate that, in mammals, Gli1 is not required for Shh signaling and that Gli2 mediates inappropriate activation of the pathway due to loss of the negative regulator Ptc. ..
- Chamberlain C, Jeong J, Guo C, Allen B, McMahon A. Notochord-derived Shh concentrates in close association with the apically positioned basal body in neural target cells and forms a dynamic gradient during neural patterning. Development. 2008;135:1097-106 pubmed publisher..This study, in which we directly observe, measure, localize and modify notochord-derived Shh ligand in the context of neural patterning, provides several new insights into mechanisms of Shh morphogen action...
- Agalliu D, Takada S, Agalliu I, McMahon A, Jessell T. Motor neurons with axial muscle projections specified by Wnt4/5 signaling. Neuron. 2009;61:708-20 pubmed publisher..Thus, two dorsoventral signaling pathways, mediated by Shh and Wnt4/5, are required to establish an early binary divergence in motor neuron columnar identity. ..
- Zeng H, Hoover A, Liu A. PCP effector gene Inturned is an important regulator of cilia formation and embryonic development in mammals. Dev Biol. 2010;339:418-28 pubmed publisher..In conclusion, we show that PCP effector gene Intu is an important regulator of cilia formation, Hh signal transduction, and embryonic development in mammals. ..
- Dessaud E, Ribes V, Balaskas N, Yang L, Pierani A, Kicheva A, et al. Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog. PLoS Biol. 2010;8:e1000382 pubmed publisher..This suggests an alternative to conventional models of morphogen action that rely solely on the level of signalling. ..
- Liu Z, Hu X, Cai J, Liu B, Peng X, Wegner M, et al. Induction of oligodendrocyte differentiation by Olig2 and Sox10: evidence for reciprocal interactions and dosage-dependent mechanisms. Dev Biol. 2007;302:683-93 pubmed..In addition, we presented evidence that the control of oligodendrocyte differentiation by Olig2, Sox10 and Nkx2.2 is a dosage-dependent developmental process and can be affected by both haploinsufficiency and over-dosage. ..
- Lei Q, Jeong Y, Misra K, Li S, Zelman A, Epstein D, et al. Wnt signaling inhibitors regulate the transcriptional response to morphogenetic Shh-Gli signaling in the neural tube. Dev Cell. 2006;11:325-37 pubmed..These results identify a transcriptional mechanism that integrates graded Shh and Wnt signaling to define progenitor gene expression domains and cell fates in the neural tube. ..
- Miyoshi G, Bessho Y, Yamada S, Kageyama R. Identification of a novel basic helix-loop-helix gene, Heslike, and its role in GABAergic neurogenesis. J Neurosci. 2004;24:3672-82 pubmed..These results suggest that combinations of distinct bHLH factors promote formation of distinct neuronal subtypes, thereby increasing neuronal diversity. ..
- Eggenschwiler J, Bulgakov O, Qin J, Li T, Anderson K. Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins. Dev Biol. 2006;290:1-12 pubmed..Instead, Rab23 appears to regulate subcellular localization of essential components of the Hedgehog pathway that act downstream of Smoothened and upstream of Gli proteins. ..
- Smith S, Qu H, Taleb N, Kishimoto N, Scheel D, Lu Y, et al. Rfx6 directs islet formation and insulin production in mice and humans. Nature. 2010;463:775-80 pubmed publisher..These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate beta-cells for patients with diabetes. ..
- Huangfu D, Liu A, Rakeman A, Murcia N, Niswander L, Anderson K. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature. 2003;426:83-7 pubmed..Our data show that IFT machinery has an essential and vertebrate-specific role in Hedgehog signal transduction. ..
- Pattyn A, Simplicio N, van Doorninck J, Goridis C, Guillemot F, Brunet J. Ascl1/Mash1 is required for the development of central serotonergic neurons. Nat Neurosci. 2004;7:589-95 pubmed..Thus Ascl1, which is essential for noradrenergic differentiation, is also a determinant of the serotonergic phenotype. ..
- Jin J, Gu S, McKinney P, Ding J. Expression and functional analysis of Tgif during mouse midline development. Dev Dyn. 2006;235:547-53 pubmed..One interpretation of these results is that the loss of TGIF function is compensated by other TGF-beta antagonists such as c-Ski and SnoN during vertebrate anterior neural development. ..
- Jacob J, Storm R, Castro D, Milton C, Pla P, Guillemot F, et al. Insm1 (IA-1) is an essential component of the regulatory network that specifies monoaminergic neuronal phenotypes in the vertebrate hindbrain. Development. 2009;136:2477-85 pubmed publisher..Thus, Insm1 regulates the synthesis of distinct monoaminergic neurotransmitters by acting combinatorially with, or independently of, Ascl1 in specific monoaminergic populations. ..
- Wijgerde M, McMahon J, Rule M, McMahon A. A direct requirement for Hedgehog signaling for normal specification of all ventral progenitor domains in the presumptive mammalian spinal cord. Genes Dev. 2002;16:2849-64 pubmed..Thus, Hh signaling is essential for organizing ventral cell pattern, possibly through the control of differential cell affinities. ..
- Pfaff S, Mendelsohn M, Stewart C, Edlund T, Jessell T. Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation. Cell. 1996;84:309-20 pubmed..These results show that ISL1 is required for the generation of motor neurons and suggest that motor neuron generation is required for the subsequent differentiation of certain interneurons. ..
- Nishimura W, Rowan S, Salameh T, Maas R, Bonner Weir S, Sell S, et al. Preferential reduction of beta cells derived from Pax6-MafB pathway in MafB deficient mice. Dev Biol. 2008;314:443-56 pubmed publisher..Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation. ..
- Endoh Yamagami S, Evangelista M, Wilson D, Wen X, Theunissen J, Phamluong K, et al. The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development. Curr Biol. 2009;19:1320-6 pubmed publisher..These results suggest a role for Kif7 in coordinating Hh signal transduction at the tip of cilia and preventing Gli3 cleavage into a repressor form in the presence of Hh. ..
- Vokes S, Ji H, Wong W, McMahon A. A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb. Genes Dev. 2008;22:2651-63 pubmed publisher..These studies provide the first comprehensive characterization of the transcriptional output of a Shh-patterning process in the mammalian embryo and a framework for elaborating regulatory networks in the developing limb. ..
- Liu A, Wang B, Niswander L. Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors. Development. 2005;132:3103-11 pubmed..In summary, our results indicate that IFT function is crucial in the control of both the positive and negative transcriptional activities of Gli proteins, and essential for Hh ligand-induced signaling cascade. ..
- Svärd J, Heby Henricson K, Henricson K, Persson Lek M, Rozell B, Lauth M, et al. Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway. Dev Cell. 2006;10:187-97 pubmed..Our data demonstrate that, in striking contrast to Drosophila, in mammals, Sufu has a central role, and its loss of function leads to potent ligand-independent activation of the Hh pathway. ..
- Ericson J, Rashbass P, Schedl A, Brenner Morton S, Kawakami A, van Heyningen V, et al. Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell. 1997;90:169-80 pubmed..2. Pax6 establishes distinct ventral progenitor cell populations and controls the identity of motor neurons and ventral interneurons, mediating graded Shh signaling in the ventral spinal cord and hindbrain. ..
- Motoyama J, Milenkovic L, Iwama M, Shikata Y, Scott M, Hui C. Differential requirement for Gli2 and Gli3 in ventral neural cell fate specification. Dev Biol. 2003;259:150-61 pubmed..Thus, Shh signaling is mediated by overlapping but distinct functions of Gli2 and Gli3, and their relative contributions vary along the rostral-caudal axis. ..
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