Phox2b

Summary

Gene Symbol: Phox2b
Description: paired-like homeobox 2b
Alias: Dilp1, NBPhox, Pmx2b, Px2b, paired mesoderm homeobox protein 2B, GENA 269, PHOX2B homeodomain protein, dilated pupils 1, neuroblastoma Phox, paired mesoderm homeobox 2b
Species: mouse
Products:     Phox2b

Top Publications

  1. Gut P, Huber K, Lohr J, Brühl B, Oberle S, Treier M, et al. Lack of an adrenal cortex in Sf1 mutant mice is compatible with the generation and differentiation of chromaffin cells. Development. 2005;132:4611-9 pubmed
    ..5. However, already at E12.5 the 'adrenal' region in Sf1-/- mice is occupied by fewer PHOX2B+ and TH+ SA cells as well as SOX10+ neural crest cells...
  2. Gaufo G, Thomas K, Capecchi M. Hox3 genes coordinate mechanisms of genetic suppression and activation in the generation of branchial and somatic motoneurons. Development. 2003;130:5191-201 pubmed
  3. Pattyn A, Morin X, Cremer H, Goridis C, Brunet J. The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Nature. 1999;399:366-70 pubmed
    ..all autonomic ganglia fail to form properly and degenerate in mice lacking the homeodomain transcription factor Phox2b, as do the three cranial sensory ganglia that are part of the autonomic reflex circuits...
  4. Storm R, Cholewa Waclaw J, Reuter K, Bröhl D, Sieber M, Treier M, et al. The bHLH transcription factor Olig3 marks the dorsal neuroepithelium of the hindbrain and is essential for the development of brainstem nuclei. Development. 2009;136:295-305 pubmed publisher
    ..We therefore propose that Olig3 can cooperate with Ptf1a to determine the fate of climbing fiber neurons of the inferior olivary nucleus. ..
  5. Tsarovina K, Reiff T, Stubbusch J, Kurek D, Grosveld F, Parlato R, et al. The Gata3 transcription factor is required for the survival of embryonic and adult sympathetic neurons. J Neurosci. 2010;30:10833-43 pubmed publisher
    ..These results demonstrate that Gata3 is continuously required for maintaining survival but not differentiation in the sympathetic neuron lineage up to mature neurons of adult animals. ..
  6. 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
    ..primary function of these proteins is to coordinate the spatial and temporal activation of the homeodomain protein Phox2b, which in turn acts as a binary switch in the selection of motor neuron or serotonergic neuronal fate...
  7. Hirsch M, Glover J, Dufour H, Brunet J, Goridis C. Forced expression of Phox2 homeodomain transcription factors induces a branchio-visceromotor axonal phenotype. Dev Biol. 2007;303:687-702 pubmed
    ..We here show that forced expression of the homeodomain protein Phox2b, shown previously to be necessary and sufficient for branchio-visceromotor neuron development, and of its ..
  8. 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. ..
  9. Coppola E, D Autréaux F, Rijli F, Brunet J. Ongoing roles of Phox2 homeodomain transcription factors during neuronal differentiation. Development. 2010;137:4211-20 pubmed publisher
    ..Here, we address this question for the paralogous paired-like homeobox genes Phox2a and Phox2b, which specify several classes of visceral neurons at the progenitor stage in the central and peripheral nervous ..

More Information

Publications62

  1. Geisen M, di Meglio T, Pasqualetti M, Ducret S, Brunet J, Chedotal A, et al. Hox paralog group 2 genes control the migration of mouse pontine neurons through slit-robo signaling. PLoS Biol. 2008;6:e142 pubmed publisher
    ..Lastly, the analysis of Phox2b-deficient mice indicated that the facial motor nucleus is a major Slit signaling source required to prevent ..
  2. 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. ..
  3. Hendershot T, Liu H, Clouthier D, Shepherd I, Coppola E, Studer M, et al. Conditional deletion of Hand2 reveals critical functions in neurogenesis and cell type-specific gene expression for development of neural crest-derived noradrenergic sympathetic ganglion neurons. Dev Biol. 2008;319:179-91 pubmed publisher
    ..Hand2 has a pivotal function in a non-linear cross-regulatory network of DNA binding proteins that affect cell autonomous control of differentiation and cell type-specific gene expression. ..
  4. Huber K, Brühl B, Guillemot F, Olson E, Ernsberger U, Unsicker K. Development of chromaffin cells depends on MASH1 function. Development. 2002;129:4729-38 pubmed
    ..Most adrenal medullary cells in Mash1(-/-) mice identified by Phox2b immunoreactivity, lack the catecholaminergic marker tyrosine hydroxylase...
  5. Potzner M, Tsarovina K, BINDER E, Penzo Méndez A, Lefebvre V, Rohrer H, et al. Sequential requirement of Sox4 and Sox11 during development of the sympathetic nervous system. Development. 2010;137:775-84 pubmed publisher
    ..As a consequence, sympathetic ganglia were rudimentary in the adult and sympathetic innervation of target tissues was impaired leading to severe dysautonomia. ..
  6. Pla P, Hirsch M, Le Crom S, Reiprich S, Harley V, Goridis C. Identification of Phox2b-regulated genes by expression profiling of cranial motoneuron precursors. Neural Dev. 2008;3:14 pubmed publisher
    ..2 and Phox2b. Phox2b in particular plays a key role in the specification of branchiomotor neurons...
  7. Dubreuil V, Hirsch M, Pattyn A, Brunet J, Goridis C. The Phox2b transcription factor coordinately regulates neuronal cell cycle exit and identity. Development. 2000;127:5191-201 pubmed
    ..by both loss- and gain-of-function experiments that the neuronal-subtype-specific homeodomain transcription factor Phox2b drives progenitor cells to become post-mitotic...
  8. Tsarovina K, Pattyn A, Stubbusch J, Muller F, van der Wees J, Schneider C, et al. Essential role of Gata transcription factors in sympathetic neuron development. Development. 2004;131:4775-86 pubmed
    ..from neural crest precursors by a network of crossregulatory transcription factors, which includes Mash1, Phox2b, Hand2 and Phox2a...
  9. Ren S, Angrand P, Rijli F. Targeted insertion results in a rhombomere 2-specific Hoxa2 knockdown and ectopic activation of Hoxa1 expression. Dev Dyn. 2002;225:305-15 pubmed
    ..They also provide a molecular basis for the interpretation of unexpected Hox knockout phenotypes in which the targeted selectable marker is retained in the locus. ..
  10. Davenne M, Maconochie M, Neun R, Pattyn A, Chambon P, Krumlauf R, et al. Hoxa2 and Hoxb2 control dorsoventral patterns of neuronal development in the rostral hindbrain. Neuron. 1999;22:677-91 pubmed
  11. Fode C, Gradwohl G, Morin X, Dierich A, LeMeur M, Goridis C, et al. The bHLH protein NEUROGENIN 2 is a determination factor for epibranchial placode-derived sensory neurons. Neuron. 1998;20:483-94 pubmed
    ..Interestingly, the homeobox gene Phox2a is activated independently of ngn2 in epibranchial placodes, suggesting that neuronal fate and neuronal subtype identity may be specified independently in cranial sensory ganglia. ..
  12. Pattyn A, Goridis C, Brunet J. Specification of the central noradrenergic phenotype by the homeobox gene Phox2b. Mol Cell Neurosci. 2000;15:235-43 pubmed
    The closely related homeobox genes Phox2a and Phox2b are expressed in all central and peripheral noradrenergic neurons...
  13. Tiveron M, Pattyn A, Hirsch M, Brunet J. Role of Phox2b and Mash1 in the generation of the vestibular efferent nucleus. Dev Biol. 2003;260:46-57 pubmed
    ..Here, we demonstrate that the inner ear efferents depend on Phox2b for their differentiation, behaving in that respect like hindbrain visceral and branchial motor neurons...
  14. Garel S, Garcia Dominguez M, Charnay P. Control of the migratory pathway of facial branchiomotor neurones. Development. 2000;127:5297-307 pubmed
    ..In addition, they establish a close correlation between the expression pattern of fbm neurones and their migratory behaviour, suggesting that modifications in gene expression participate in the selection of the local migratory pathway. ..
  15. Huber K, Karch N, Ernsberger U, Goridis C, Unsicker K. The role of Phox2B in chromaffin cell development. Dev Biol. 2005;279:501-8 pubmed
    b>Phox2B, a homeodomain transcription factor closely related to Phox2A, is expressed in peripheral and central noradrenergic neurons...
  16. Young H, Bergner A, Muller T. Acquisition of neuronal and glial markers by neural crest-derived cells in the mouse intestine. J Comp Neurol. 2003;456:1-11 pubmed
    ..Previous studies have shown that undifferentiated enteric crest-derived cells are Phox2b(+)/Ret(+)/p75(+)/Sox10(+), and at embryonic day (E) 10...
  17. Pattyn A, Hirsch M, Goridis C, Brunet J. Control of hindbrain motor neuron differentiation by the homeobox gene Phox2b. Development. 2000;127:1349-58 pubmed
    ..We provide genetic evidence that the paired-like homeodomain protein Phox2b is required for the formation of all branchial and visceral, but not somatic, motor neurons in the hindbrain...
  18. Pattyn A, Morin X, Cremer H, Goridis C, Brunet J. Expression and interactions of the two closely related homeobox genes Phox2a and Phox2b during neurogenesis. Development. 1997;124:4065-75 pubmed
    ..We now report on the characterization of Phox2b, a close relative of Phox2a, with an identical homeodomain...
  19. Gavalas A, Ruhrberg C, Livet J, Henderson C, Krumlauf R. Neuronal defects in the hindbrain of Hoxa1, Hoxb1 and Hoxb2 mutants reflect regulatory interactions among these Hox genes. Development. 2003;130:5663-79 pubmed
    ..Therefore, we have delineated the functional requirements in hindbrain neuronal patterning that follow the establishment of the genetic regulatory hierarchy between Hoxa1, Hoxb1 and Hoxb2. ..
  20. Ohsawa R, Ohtsuka T, Kageyama R. Mash1 and Math3 are required for development of branchiomotor neurons and maintenance of neural progenitors. J Neurosci. 2005;25:5857-65 pubmed
  21. Coppola E, Pattyn A, Guthrie S, Goridis C, Studer M. Reciprocal gene replacements reveal unique functions for Phox2 genes during neural differentiation. EMBO J. 2005;24:4392-403 pubmed
    The paralogous paired-like homeobox genes Phox2a and Phox2b are involved in the development of specific neural subtypes in the central and peripheral nervous systems...
  22. Gaufo G, Wu S, Capecchi M. Contribution of Hox genes to the diversity of the hindbrain sensory system. Development. 2004;131:1259-66 pubmed
    ..More generally, these findings contribute to our understanding of how Hox genes specifically control cellular diversity in the developing organism ..
  23. Sieber M, Storm R, Martinez de la Torre M, Muller T, Wende H, Reuter K, et al. Lbx1 acts as a selector gene in the fate determination of somatosensory and viscerosensory relay neurons in the hindbrain. J Neurosci. 2007;27:4902-9 pubmed
    ..In Lbx1 mutant mice, viscerosensory relay neurons are specified at the expense of somatosensory relay neurons. Thus Lbx1 expression distinguishes between the somatosensory or viscerosensory fate of relay neurons. ..
  24. Qian Y, Shirasawa S, Chen C, Cheng L, Ma Q. Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1. Genes Dev. 2002;16:1220-33 pubmed
    ..Together, our studies demonstrate a central role for Rnx and Tlx-1 in the development of two major classes of relay sensory neurons, somatic and visceral. ..
  25. Coppola E, Rallu M, Richard J, Dufour S, Riethmacher D, Guillemot F, et al. Epibranchial ganglia orchestrate the development of the cranial neurogenic crest. Proc Natl Acad Sci U S A. 2010;107:2066-71 pubmed publisher
  26. Morikawa Y, D Autréaux F, Gershon M, Cserjesi P. Hand2 determines the noradrenergic phenotype in the mouse sympathetic nervous system. Dev Biol. 2007;307:114-26 pubmed
    ..Our data suggest that the major role of Hand2 during SNS development is to permit sympathetic neurons to acquire a catecholaminergic phenotype. ..
  27. Theil T, Ariza McNaughton L, Manzanares M, Brodie J, Krumlauf R, Wilkinson D. Requirement for downregulation of kreisler during late patterning of the hindbrain. Development. 2002;129:1477-85 pubmed
    ..We propose that the requirement for the downregulation of segmental kreisler expression prior to neuronal differentiation reflects the stage-specific roles of this gene and its targets. ..
  28. Samad O, Geisen M, Caronia G, Varlet I, Zappavigna V, Ericson J, et al. Integration of anteroposterior and dorsoventral regulation of Phox2b transcription in cranial motoneuron progenitors by homeodomain proteins. Development. 2004;131:4071-83 pubmed
    ..We have previously shown that in ventral rhombomere (r)4 of Hoxb1 and Hoxb2 mutant mouse embryos, Phox2b expression is not properly maintained in the visceral motoneuron progenitor domain (pMNv), resulting in a switch ..
  29. Grillet N, Dubreuil V, Dufour H, Brunet J. Dynamic expression of RGS4 in the developing nervous system and regulation by the neural type-specific transcription factor Phox2b. J Neurosci. 2003;23:10613-21 pubmed
    ..This expression pattern overlaps extensively with that of the paired-like homeodomain protein Phox2b, a determinant of neuronal identity...
  30. Gaufo G, Flodby P, Capecchi M. Hoxb1 controls effectors of sonic hedgehog and Mash1 signaling pathways. Development. 2000;127:5343-54 pubmed
    ..The findings reported here provide evidence for a genetic cascade in which an AP-specified transcription factor, Hoxb1, controls the commitment and specification of neurons derived from both alar and basal plates of r4. ..
  31. Manzanares M, Trainor P, Nonchev S, Ariza McNaughton L, Brodie J, Gould A, et al. The role of kreisler in segmentation during hindbrain development. Dev Biol. 1999;211:220-37 pubmed
    ..Analysis of Phox2b expression shows that some aspects of later neurogenesis in r6 are altered, which may be associated with the ..
  32. Qian Y, Fritzsch B, Shirasawa S, Chen C, Choi Y, Ma Q. Formation of brainstem (nor)adrenergic centers and first-order relay visceral sensory neurons is dependent on homeodomain protein Rnx/Tlx3. Genes Dev. 2001;15:2533-45 pubmed
    ..and can be prospectively identified by combinatorial expression of two homeobox genes, Rnx and Phox2 (Phox2a or Phox2b). It was previously shown that Rnx-deficient mice die from respiratory failure...
  33. Chang S, Yan Y, Shi Y, Liu Y, Takahashi H, Liu F. Region- and cell type-selective expression of the evolutionarily conserved Nolz-1/zfp503 gene in the developing mouse hindbrain. Gene Expr Patterns. 2011;11:525-32 pubmed publisher
    ..cells were organized as distinct cell clusters, and they were largely non-overlapped with either Pax2-positive or Phox2b-positive domains...
  34. de Graaff E, Srinivas S, Kilkenny C, D AGATI V, Mankoo B, Costantini F, et al. Differential activities of the RET tyrosine kinase receptor isoforms during mammalian embryogenesis. Genes Dev. 2001;15:2433-44 pubmed
    ..Our findings show that RET9 and RET51 have different signaling properties in vivo and define specific temporal and spatial requirements of c-Ret function during renal development and histogenesis of the enteric nervous system. ..
  35. Aroca P, Lorente Cánovas B, Mateos F, Puelles L. Locus coeruleus neurons originate in alar rhombomere 1 and migrate into the basal plate: Studies in chick and mouse embryos. J Comp Neurol. 2006;496:802-18 pubmed
    ..in the hindbrain, using as markers the key noradrenergic marker gene Dbh and the transcription factors Phox2a and Phox2b (upstream of Dbh)...
  36. Borghini S, Bachetti T, Fava M, Di Duca M, Cargnin F, Fornasari D, et al. The TLX2 homeobox gene is a transcriptional target of PHOX2B in neural-crest-derived cells. Biochem J. 2006;395:355-61 pubmed
    The TLX2 (HOX11L1, Ncx, Enx) and PHOX2B genes encode transcription factors crucial in the development of neural-crest-derived cells, leading to ANS (autonomic nervous system) specific neuronal lineages...
  37. Honma Y, Araki T, Gianino S, Bruce A, Heuckeroth R, Johnson E, et al. Artemin is a vascular-derived neurotropic factor for developing sympathetic neurons. Neuron. 2002;35:267-82 pubmed
    ..The chemoattractive properties of ARTN were confirmed by the demonstration that sympathetic neuroblasts migrate and project axons toward ARTN-soaked beads implanted into mouse embryos. ..
  38. Alfonsi F, Filippi P, Salaün D, Delapeyrière O, Durbec P. LIFR beta plays a major role in neuronal identity determination and glial differentiation in the mouse facial nucleus. Dev Biol. 2008;313:267-78 pubmed
    ..We also show that LIFR beta is implicated in astrocyte and oligodendrocyte differentiation, specifically within the facial nucleus. ..
  39. Gallego J, Dauger S. PHOX2B mutations and ventilatory control. Respir Physiol Neurobiol. 2008;164:49-54 pubmed publisher
    The transcription factor PHOX2B is essential for the development of the autonomic nervous system...
  40. Makki N, Capecchi M. Hoxa1 lineage tracing indicates a direct role for Hoxa1 in the development of the inner ear, the heart, and the third rhombomere. Dev Biol. 2010;341:499-509 pubmed publisher
  41. Hirsch M, D Autréaux F, Dymecki S, Brunet J, Goridis C. A Phox2b::FLPo transgenic mouse line suitable for intersectional genetics. Genesis. 2013;51:506-14 pubmed publisher
    b>Phox2b is a transcription factor expressed in the central and peripheral neurons that control cardiovascular, respiratory, and digestive functions and essential for their development...
  42. Liu Z, Li H, Hu X, Yu L, Liu H, Han R, et al. Control of precerebellar neuron development by Olig3 bHLH transcription factor. J Neurosci. 2008;28:10124-33 pubmed publisher
    ..Therefore, Olig3 plays an important role in the fate specification and differentiation of caudal RL-derived neurons. ..
  43. Rüdiger R, BINDER E, Tsarovina K, Schmidt M, Reiff T, Stubbusch J, et al. In vivo role for CREB signaling in the noradrenergic differentiation of sympathetic neurons. Mol Cell Neurosci. 2009;42:142-51 pubmed publisher
  44. Bollen B, Ramanantsoa N, Naert A, Matrot B, Van den Bergh O, D Hooge R, et al. Emotional disorders in adult mice heterozygous for the transcription factor Phox2b. Physiol Behav. 2015;141:120-6 pubmed publisher
    b>Phox2b is an essential transcription factor for the development of the autonomic nervous system...
  45. Anderson R, Stewart A, Young H. Phenotypes of neural-crest-derived cells in vagal and sacral pathways. Cell Tissue Res. 2006;323:11-25 pubmed
    ..examine the phenotype of neural-crest-derived cells in vagal and sacral pathways, we used antisera to Sox10, p75, Phox2b, and Hu, and transgenic mice in which the expression of green fluorescent protein was under the control of the Ret ..
  46. Ramanantsoa N, Vaubourg V, Matrot B, Vardon G, Dauger S, Gallego J. Effects of temperature on ventilatory response to hypercapnia in newborn mice heterozygous for transcription factor Phox2b. Am J Physiol Regul Integr Comp Physiol. 2007;293:R2027-35 pubmed
    ..The main cause of CCHS is a mutation in the PHOX2B gene, which encodes a transcription factor involved in the development of autonomic medullary reflex pathways...
  47. Barlow A, de Graaff E, Pachnis V. Enteric nervous system progenitors are coordinately controlled by the G protein-coupled receptor EDNRB and the receptor tyrosine kinase RET. Neuron. 2003;40:905-16 pubmed
    ..Our data provide strong evidence that the coordinate and balanced interaction between receptor tyrosine kinases and G protein-coupled receptors controls the development of the nervous system in mammals. ..
  48. Chen Y, Takano Maruyama M, Fritzsch B, Gaufo G. Hoxb1 controls anteroposterior identity of vestibular projection neurons. PLoS ONE. 2012;7:e34762 pubmed publisher
  49. Jarrar W, Dias J, Ericson J, Arnold H, Holz A. Nkx2.2 and Nkx2.9 are the key regulators to determine cell fate of branchial and visceral motor neurons in caudal hindbrain. PLoS ONE. 2015;10:e0124408 pubmed publisher
    ..2 and Nkx2.9 proteins play no role in the development of branchiovisceral motor neurons in hindbrain rostral to rhombomere 4. ..
  50. Croizier S, Prevot V, Bouret S. Leptin Controls Parasympathetic Wiring of the Pancreas during Embryonic Life. Cell Rep. 2016;15:36-44 pubmed publisher
  51. Moriguchi T, Takako N, Hamada M, Maeda A, Fujioka Y, Kuroha T, et al. Gata3 participates in a complex transcriptional feedback network to regulate sympathoadrenal differentiation. Development. 2006;133:3871-81 pubmed
    ..Additionally, mRNA analyses of purified chromaffin cells from Gata3 mutants show that levels of Mash1, Hand2 and Phox2b (postulated upstream regulators of Gata3) as well as terminally differentiated SA lineage products (tyrosine ..
  52. Liu Z, Shi M, Hu Z, Zheng M, Du F, Zhao G, et al. A refined map of early gene expression in the dorsal rhombomere 1 of mouse embryos. Brain Res Bull. 2010;82:74-82 pubmed publisher
    ..of several genes expressed in the mantle zone of the dorsal r1, including Lmx1b, Lhx2, Lhx9, Phox2a and Phox2b. Taken together, our gene expression data identify a refined subdivision of the dorsal r1 with four distinct ..
  53. Nagashimada M, Ohta H, Li C, Nakao K, Uesaka T, Brunet J, et al. Autonomic neurocristopathy-associated mutations in PHOX2B dysregulate Sox10 expression. J Clin Invest. 2012;122:3145-58 pubmed publisher
    ..syndrome (CCHS) harboring a nonpolyalanine repeat expansion mutation of the Paired-like homeobox 2b (PHOX2B) gene, but the molecular mechanism of pathogenesis remains unknown...